This group represents a predicted rubisco-cytochrome methylase, MET type.Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme in photosynthetic carbon assimilation. The enzyme is composed of large (rbcL) and small (rbcS) subunits, and has been found in algae, cryptophytes and land plants. This entry represents the small subunit, N-methyltransferase I, of Rubisco from cryptophytes. Cryptophytes posses a DNA-containing nucleomorph in addition to a nucleus, mitochondria and plastids; these dwarf nucleomorphs are remnants of red-algae symbionts [, ].
Free methionine-R-sulfoxide reductases are a family of GAF domain-containing proteins that have been shown to catalyse the reversible oxidation-reduction of the R-enantiomer of free methionine sulfoxide to methionine []. This entry represents a conserved site within the GAF domain section of these proteins.
Cystathionine beta-lyase (alternate name: beta-cystathionase) is one of several pyridoxal-dependent enzymes of cysteine, methionine, and homocysteine metabolism. This enzyme is involved in the biosynthesis of Met from Cys [].
This group of sequences represent cystathionine beta-lyase (alternate name: beta-cystathionase), one of several pyridoxal-dependent enzymes of cysteine, methionine, and homocysteine metabolism. This enzyme is involved in the biosynthesis of Met from Cys.
Granzyme M is a chymotrypsin-like serine protease that preferentially cuts its substrates after Met or Leu []. It has been shown to be involved in inflammation, tumour immunity and cell death [].
Mucin-20 (MUC20) was identifiied as a gene that is up-regulated in the renal tissues of patients with immunoglobulin A nephropathy []. It is a regulator of the Met signaling cascade. MUC20 associates with Met which is the hepatocyte growth factor (HGF) receptor, and has a role in suppressing the Grb2-Ras pathway. Production of MUC20 reduced HGF-induced matrix metalloproteinase expression and proliferation, which require the Grb2-Ras pathway [].
This is a cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found in plexin () []. Two copies of the repeat are found in mahogany protein. A related Caenorhabditis elegans protein () contains four copies of the repeat, while the Met receptor contains a single copy of the repeat.
This entry includes hepatocyte growth factor (HGF; also called scatter factor) and HGF-like proteins (also known as macrophage stimulatory protein, MST1). Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration []. HGF is essential for placental, liver, and muscle development, whereas MST1 is not required for embryogenesis, fertility, or wound healing. Genes for HGF and its receptor, the Met tyrosine kinase, are close together on chromosome 7, so that polysomy of chromosome 7 may contribute to malignancy through overproduction of both molecules. MST1 and its receptor, the Ron tyrosine kinase, are close together on chromosome 3. HGF and MST1 are closely related to plasminogen, having similar domain architecture: signal sequence followed by a PAN (formerly apple) domain, four (rather than five) kringle domains, and a trypsin domain, which appears to lack any peptidase activity.
The IPT (Ig-like, plexins, transcription factors) domain has an immunoglobulin like fold []. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering) [].
Phytocyanins are blue copper proteins found in chloropasts of higher plants. They can be further subdivided into uclacyanins, stellacyanins, plantacyanins, and early nodulins. Stellacyanins have a blue copper coordinated by two His, one Cys and one Gln. In plantacyanins and uclacyanins, the ligands of the type-I Cu sites are two His, one Cys and one Met [, , , ]. Early nodulins lack amino acid residues that coordinate Cu, so they are believed to be involved in unknown processes without binding Cu [].
This entry includes the CoxC protein from the CO-metabolizing bacterium Oligotropha carboxidovorans []. In the CoxC and CoxH proteins, the LytTR DNA-binding transcriptional regulator domain []is found in association with MHYT, a recently described sensor domain, which contains six transmembrane segments carrying conserved His and Met residues []. The coxCand coxHgenes flank the operon encoding the CO dehydrogenase and are involved in transcriptional regulaton of the autotrophic metabolism in Oligotropha carboxidovorans [].
This is the C-terminal domain of N-formyltransferase from Francisella tularensis. N-formylated sugars are observed on O-antigens of pathogenic Gram-negative bacteria. This C-terminal domain is responsible for dimerization. In particular, the beta hairpin motif present in the domain helps create a subunit-subunit interface. The dimeric interface is characterized by a hydrophobic patch formed by Ile 195, Leu 197, Val 201, Met 203, Ile 207, Phe 223, Val 231, Val 233, Leu 235, and Leu 237 from both monomers [].
This entry represents a region of about 41 amino acids found in a number of small proteins in a wide range of bacteria. The region usually begins with the initiator Met and contains two CxxC motifs separated by 17 amino acids. One protein in this entry has been noted as a putative regulatory protein, designated FmdB []. Most proteins in this entry have a C-terminal region containing highly degenerate sequence.
All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys. Alpha-N-methyltransferase methylates the N terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. It catalyses mono-, di- or tri-methylation of the exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif [, , ]. Some of the substrates may be primed by NTMT2-mediated monomethylation [].
This entry represents S-adenosyl-L-methionine (SAM) hydrolases (), which catalyse the hydrolysis of S-adenosyl-L-methionine, cleaving it to form L-homoserine and methylthioadenosine. This enzyme is produced by Bacteriophage T3, which infects Escherichia coli cells. SAM hydrolase can remove S-adenosylmethionine from the E. coli cell, thereby inhibiting a variety of SAM-related activities, such as dam and dcm methylase-directed DNA modifications and the synthesis of spermidine from putrescine []. Expression of SAM hydrolase in T3-transformed E. coli induces the met regulon by cleaving the SAM co-repressor to form 5'-methylthioadenosine, which is then cleaved to produce 5-methylthioribose [].
The Ror family of receptor tyrosine kinases consists of two structurally related proteins, Ror1 and Ror2. Ror1 is a pseudokinase that acts as a substrate for the oncogenic tyrosine kinase Met []. It is expressed during development []. It shows no significant expression in normal adult tissues, but it is selectively overexpressed in a number of malignancies []. Ror2 functions as a Wnt receptor required to maintain basal NMDAR-mediated synaptic transmission []. For a time its ligand remained elusive, hence the name receptor tyrosine kinase-like orphan receptor-2 (Ror2). It is now established that Wnt5A acts a ligand for Ror2 [].
Hepatocyte growth factor (HGF) is an activating ligand of the tyrosine kinase receptor Met. It activates Met by binding and promoting its dimerisation. This activation has been linked to promoting the invasive growth of many tumour types []. HGF acts as growth factor for a broad spectrum of tissues and cell types and has no detectable protease activity [].Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39). A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information [].
FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity []. It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two beta sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions [].
FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity []. It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two beta sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions [].
NmrA is a negative transcriptional regulator of various fungi, involved in the post-translational modulation of the GATA-type transcription factor AreA []. NmrA lacks the canonical GXXGXXG NAD-binding motif and has altered residues at the catalytic triad, including a Met instead of the critical Tyr residue. NmrA may bind nucleotides but appears to lack any dehydrogenase activity. It lacks most of the active site residues of the SDR (short-chain dehydrogenases/reductases) family, but has an NAD(P)-binding motif similar to the extended SDR family, GXXGXXG [].This domain can also be found in other atypical SDRs, such as HSCARG (an NADPH sensor) []and PCBER (phenylcoumaran benzylic ether reductase) [].
NosL is one of the accessory proteins of the nos (nitrous oxide reductase) gene cluster. NosL is a monomeric protein of 18,540 MW that specifically and stoichiometrically binds Cu(I). The copper ion in NosL is ligated by a Cys residue, and one Met and one His are thought to serve as the other ligands. It is possible that NosL is a copper chaperone involved in metallocentre assembly [].This entry also contains HTH-type transcriptional repressors, including YcnK. YcnK may act as a negative transcriptional regulator of YcnJ inthe presence of copper and may use copper as a corepressor. The gene, ycnK, is significantly induced under copper-limiting conditions [].
This entry represents the methionine S-methyltransferase () family, which catalyse the S-methylmethionine (SMM) biosynthesis from adenosyl-L-homocysteine (AdoMet) and methionine []. All flowering plants produce S-methylmethionine (SMM) from Met and have a separate mechanism to convert SMM back to Met. The functions of SMM and the reasons for its interconversion with Met are unknown []. Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [, , ]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [, , ]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [, , ]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
The oxidation of methionine residues in proteins is considered to be one of the consequences of oxidative damage to cells, which in many cases leads to the loss of biological activity. Peptide methionine sulphoxide reductase (Msr) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulphoxide, (MetO), to methionine []. Methionine (Met) can be oxidised to the R and S diastereomers of methionine sulfoxide (MetO). Methionine sulfoxide reductases A (MsrA) and B (MsrB) reduce MetO back to Met in a stereospecific manner, acting on the S and R forms, respectively. Msr is present in most living organisms [, ].Many bacteria, particularly pathogens, possess methionine sulfoxide reductase MsrA and MsrB as a fusion form (MsrAB) []. This entry includes MsrB and the fusion form of these enzymes.
Cytochrome c oxidase assembly protein is essential for the assembly of functional cytochrome oxidase protein. In eukaryotes it is an integral protein of the mitochondrial inner membrane. Cox11 is essential for the insertion of Cu(I) ions to form the CuB site. This is essential for the stability of other structures in subunit I, for example haems a and a3, and the magnesium/manganese centre. Cox11 is probably only required in sub-stoichiometric amounts relative to the structural units []. The C-terminal region of the protein is known to form a dimer. Each monomer coordinates one Cu(I) ion via three conserved cysteine residues (111, 208 and 210) in Saccharomyces cerevisiae (). Met 224 is also thought to play a role in copper transfer or stabilising the copper site [].
These enzymes are involved in nitrate assimilation in the denitrification pathway. The 3D structure of the copper-containing nitrite reductase (NIR) from Achromobacter cycloclastes has been determined to 2.3A resolution []. The enzyme is a trimer, each monomer of which contains two Greek key β-barrel domains (similar to that of plastocyanin) and houses two copper sites. The two copper atoms in the monomer comprise a type I copper site (Cu-I: two His, one Cys and one Met ligand) that plays a crucial role for electron transfer from pseudoazurin to the type II copper site (Cu-II: three His and one solvent ligand), the catalytic centre of NIR for the reduction ofnitrite. The Cu-II site lies at the bottom of a 12A deep solvent channel and is the site to which the substrate (NO2-) binds [].
Cytochrome c oxidase assembly protein is essential for the assembly of functional cytochrome oxidase protein. In eukaryotes it is an integral protein of the mitochondrial inner membrane. Cox11 is essential for the insertion of Cu(I) ions to form the CuB site. Thisis essential for the stability of other structures in subunit I, for example haems a and a3, and the magnesium/manganese centre. Cox11 is probably only required in sub-stoichiometric amounts relative to the structural units []. The C-terminal region of the protein is known to form a dimer. Each monomer coordinates one Cu(I) ion via three conserved cysteine residues (111, 208 and 210) in Saccharomyces cerevisiae (). Met 224 is also thought to play a role in copper transfer or stabilising the copper site [].The copper binding motif is composed of two highly conserved cysteines and is located on one side of a β-barrel structure [].
Aspartate kinase () (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine [].In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.This entry represents a region encoding aspartate kinase activity found in both the monofunctional and bifunctional enzymes.Synonym(s): Aspartokinase
MetR, a member of the LysR family, is a positive regulator for the metA, metE, metF, and metH genes []. The sulfur-containing amino acid methionine is the universal initiator of protein synthesis in all known organisms and its derivative S-adenosylmethionine (SAM) and autoinducer-2 (AI-2) are involved in various cellular processes. SAM plays a central role as methyl donor in methylation reactions, which are essential for the biosynthesis of phospholipids, proteins, DNA and RNA. The interspecies signaling molecule AI-2 is involved in cell-cell communication process (quorum sensing) and gene regulation in bacteria. Although methionine biosynthetic enzymes and metabolic pathways are well conserved in bacteria, the regulation of methionine biosynthesis involves various regulatory mechanisms. In Escherichia coli and Salmonella enterica serovar Typhimurium, MetJ and MetR regulate the expression of methionine biosynthetic genes []. The MetJ repressor negatively regulates the E. coli met genes, except for metH []. Several of these genes are also under the positive control of MetR with homocysteine as a co-inducer. In Bacillus subtilis, the met genes are controlled by S-box termination-antitermination system. This substrate-binding domain shows significant homology to the type 2 periplasmic binding proteins (PBP2).The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction [, , ].
Binding of a specific DNA fragment and S-adenosyl methionine (SAM) co-repressor molecules to the Escherichia coli methionine repressor (MetJ) leads to a significant reduction in dynamic flexibility of the ternary complex, with considerable entropy-enthalpy compensation, not necessarily involving any overall conformational change []. MetJ is a regulatory protein which when combined with S-adenosylmethionine (SAM) represses the expression of the methionine regulon and of enzymes involved in SAM synthesis. It is also autoregulated.MetJ binds arrays of two to five adjacent copies of an eight base-pair 'metbox' sequence. MetJ forms sufficiently strong interactions with the sugar-phosphate backbone to accomodate sequence variation in natural operators. However, it is very sensitive to particular base changes in the operator. MetJ exists as a homodimer [, , ].The crystal structure of the met repressor-operator complex shows two dimeric repressor molecules bound to adjacent sites 8 base pairs apart on an 18-base-pair DNA fragment. Sequence specificity is achieved by insertion of double-stranded antiparallel protein β-ribbons into the major groove of B-form DNA, with direct hydrogen-bonding between amino-acid side chains and the base pairs. The repressor also recognises sequence-dependent distortion or flexibility of the operator phosphate backbone, conferring specificity even for inaccessible base pairs [].
Peptidase family M54 (archaemetzincin or archaelysin) is a zinc-dependent aminopeptidase that contains the consensus zinc-binding sequence HEXXHXXGXXH/D and a conserved Met residue at the active site, and is thus classified as a metzincin. Archaemetzincins, first identified in archaea, are also found in bacteria and eukaryotes, including two human members, archaemetzincin-1 and -2 (AMZ1 and AMZ2). AMZ1 is mainly found in the liver and heart while AMZ2 is primarily expressed in testis and heart; both have been reported to be aminopeptidases, degrading synthetic substrates and peptides. The peptidase M54 family contains an extended metzincin concensus sequence of HEXXHXXGX3CX4CXMX17CXXC such that a second zinc ion is bound to four cysteines, thus resembling a zinc finger. Phylogenetic analysis of this family reveals a complex evolutionary process involving a series of lateral gene transfer, gene loss and genetic duplication events [, ].Archaemetzincin (from Mycococcus xanthus) seem to have evolved into a zinc-binding transcription factor fulfilling only a structuralrole [, ]. The structure of archaemetzincin from Methanopyrus kandleri has been resolved [].
Endoplasmic reticulum aminopeptidase 1 (ERAP1 or PILS; MEROPS identifier M01.018) is an aminopeptidase with a preference to release Leu or Met from the N terminus of a peptide, but can hydrolyze Phe, Tyr, Ile or Cys bonds but poorly [, ]. The aminopeptidase is insensitive to inhibition by puromycin (which inhibits cytosol alanyl aminopeptidase and dipeptidyl-peptidases II and IV) and is also known as puromycin-insensitive leucyl-specific aminopeptidase or PILS-AP [, ]. In humans, ERAP1 associates with another aminopeptidase, ERAP2, in the endoplasmic reticulum and both participate in the processing of MHC-presented peptides []. Peptides generated by degradation of proteins by the proteasome bind to a transporter associated with antigen presentation (TAP) and are exported across the plasma membrane from the cytoplasm to the endoplasmic reticulum where they are trimmed by the ERAP aminopeptidases and cystinyl aminopeptidase to be 8-11 amino acids in length which then associate with the MHC complex and beta2-microglobulin []. ERAP1 is most active with peptides 9-16 residues long, but activity drops once a peptide optimal for antigen presentation is achieved. This molecular ruler effect is achieved by binding the C terminus of the substrate peptide close to the active site []. ERAP1 may also function in blood pressure regulation because it cleaves angiotensin II to the tripeptide His-Pro-Phe via angiotensin II and IV intermediates, and converts kallidin to bradykinin []. ERAP1 has been associated with several human diseases, including ankylosing spondylitis [], psoriasis [], type 1 diabetes []and osteoporsis [].
Spore formation by the bacterium Bacillus subtilis is a stress response triggered by nutrient limitation. Two operons are strongly induced at the start of sporulation; one of them is skf (for sporulation killing factor). skf produces a killing factor which, together with a signaling protein, act cooperatively to block sister cells from sporulating and cause them to lyse, providing a source of nutrients to support the sporulation process [].The first gene of the skf operon, skfA, encodes a small peptide. SkfA induces the lysis of sibling cells that have not entered the sporulation pathway []. The product of the second gene, skfB, encodes a radical SAM enzyme. SkfB creates a sactipeptide (sulfur-to-α-carbon) crosslink of Cys-4 to Met-12 of the mature form of SkfA. In Paenibacillus larvae subsp larvae B-3650, the Met is replaced by Leu, so the modification must be different. SkfB has 2 4Fe-4S clusters, one in its radical SAM domain () and one in a region that somewhat resembles the SPASM domain () [].
Binding of a specific DNA fragment and S-adenosyl methionine (SAM) co-repressor molecules to the Escherichia coli methionine repressor (MetJ) leads to a significant reduction in dynamic flexibility of the ternary complex, with considerable entropy-enthalpy compensation, not necessarily involving any overall conformational change []. MetJ is a regulatory protein which when combined with S-adenosylmethionine (SAM) represses the expression of the methionine regulon and of enzymes involved in SAM synthesis. It is also autoregulated.MetJ binds arrays of two to five adjacent copies of an eight base-pair 'metbox' sequence. MetJ forms sufficiently strong interactions with the sugar-phosphate backbone to accomodate sequence variation in natural operators. However, it is very sensitive to particular base changes in the operator. MetJ exists as a homodimer [, , ].The crystal structure of the met repressor-operator complex shows two dimeric repressor molecules bound to adjacent sites 8 base pairs apart on an 18-base-pair DNA fragment. Sequence specificity is achieved by insertion of double-stranded antiparallel protein β-ribbons into the major groove of B-form DNA, with direct hydrogen-bonding between amino-acid side chains and the base pairs. The repressor also recognises sequence-dependent distortion or flexibility of the operator phosphate backbone, conferring specificity even for inaccessible base pairs [].
Cathepsin Z (also known as Cathepsin X , and MEROPS identifier C01.013) is predominantly a cysteine-type carboxypeptidase with limited endopeptidase or dipeptidyl-peptidase activity, mainly against synthetic substrates [, ]. The substrate specificity has been examined by peptide scanning and shows that proline is not tolerated in the P1 or P1' positions and poorly accepted in P2, and Tyr, Met and Cys are marginally prefered in P2, P1 and P1' [, ].Cathepsin X is synthesized as an inactive zymogen, but the propeptide lacks the ERFNIN motif characteristic of lysosomal cysteine peptidases. A disulfide bridge can be formed between the proregion and the enzyme which leads to inactivation of the zymogen by the formation of a reversible covalent bond with the active site residue []. From the crystal structure of the mature enzyme, a short, five-residue 'mini-loop' which includes the motif His-Xaa-Xaa-Xaa-Tyr restricts access to the S2' binding pocket, and it is the histidine that confers carboxypeptidase activity []. Rotation of the histidine ring permits dipeptidyl-peptidase substrates to bind. The presence of an exposed RGD motif allows binding to beta3-integrin []and the enzyme may have a role in cell signalling. Cathepsin X deficiency leads to accelerated cell senescence []. Cathepsin X also regulates the immune response to Helicobacter pylori infection [, ].
Among the blue copper proteins with a single type I (or "blue") mononuclearcopper site, the plant-specific phytocyanins constitute a distinct subfamilythat can be further subdivided into the families of uclacyanins, stellacyanins,plantacyanins, and early nodulins. Stellacyanins have a blue coppercoordinated by two His, one Cys and one Gln. In plantacyanins and uclacyanins,the ligands of the type-I Cu sites are two His, one Cys and one Met [, , , ]. Early nodulins lack amino acid residues that coordinate Cu, so they are believed to be involved in unknown processes without binding Cu []. Phytocyanins are found in chloropasts of higher plants.The phytocyanin domain has a core of seven polypeptide strands arranged as aβ-sandwich comprising two β-sheets, β-sheet I and β-sheet II. β-sheet I consists of three β-strands and β-sheet IIconsists of four β-strands. A disulfide bridge close the metal centre ischaracteristic for phytocyanins, in contrast to azurins, pseudoazurins, andplastocyanins, where a disulfide bond is located on the distal side of theβ-barrel. This disuldide bridge may play a crucial role in maintaining thetertiary structure of the protein and/or the formation of the copper bindingcentre because one of the His ligands of copper is followed directly by abridging Cys residue [, , , ]. Some members of this family (P93328) may not bind copper due to the lack of key residues. Some proteins known to contain a phytocyanin domain are listed below:Cucumber basic protein (CBP).Spinach basic protein (SBP).Cucumber stellacyanin (CST).Zucchini mavicyanin.Horseradish umecyanin [, ]. Some of the proteins in this family are allergens. The allergens in this family include allergens with the following designations: Amb a 3.
This family of proteins represent monomeric serralysin inhibitors of about 125 residues, which interact with specific metalloprotease which are synthesised by serralysin secretors and characterised by being plant, insect and animal pathogens. It is probable that the serralysin inhibitors protect the host from proteolysis during export of the protease. The members of this family belong to MEROPS proteinase inhibitor family I38, clan IK.X-ray crystallography of a complex between the Serratia marcescens protease, SmaPI, and the inhibitor of Erwinia chrysanthemi, Inh, reveals that Inh is folded into an eight-stranded b-barrel with an N-terminal trunk of 10 residues. Residues 1-5 occupy part of the extended active site of the proteinase, thereby preventing access of the substrate. Residues 6-10 form a linker that connects the N-terminal proteinase-binding peptide to the body of the b-barrel. The backbone carbonyl of Ser-1 interacts with the catalytic zinc; the Ser-2 side chain occupies the S1'-binding site and also forms a hydrogen bond to the carboxyl end of the catalytic Glu, whereas Leu-3 occupies the S2' recognition site. Penetration of the trunk region further than 5 residues into the substrate binding cleft appears to be prevented by the b-barrel, which itself interacts with the proteinase near its Met turn (19). Peptide mimetics of the trunk at concentrations up to about 100 mM do not inhibit the protease, demonstrating that the barrel is essential for inhibitory activity [, ].Structurally and functionally these inhibitors are closely related to the lipocalins, fatty acid-binding proteins, avidins and the enigmatic triabin.Together these five protein families constitute the calycin superfamily []. The proteins are characterised by their high specificity for small hydrophobic molecules and by their ability to form complexes with soluble macromolecules either through intramolecular disulphides or protein-protein interactions [].
Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see [].Aspartate kinase () (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine [].In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.
This entry represents the metalloprotease inhibitor I38, as well as the outer membrane lipoprotein Omp19.This family of proteins represent monomeric serralysin inhibitors of about 125 residues, which interact with specific metalloprotease which are synthesised by serralysin secretors and characterised by being plant, insect and animal pathogens. It is probable that the serralysin inhibitors protect the host from proteolysis during export of the protease. The members of this family belong to MEROPS proteinase inhibitor family I38, clan IK.X-ray crystallography of a complex between the Serratia marcescens protease, SmaPI, and the inhibitor of Erwinia chrysanthemi, Inh, reveals that Inh is folded into an eight-stranded b-barrel with an N-terminal trunk of 10 residues. Residues 1-5 occupy part of the extended active site of the proteinase, thereby preventing access of the substrate. Residues 6-10 form a linker that connects the N-terminal proteinase-binding peptide to the body of the b-barrel. The backbone carbonyl of Ser-1 interacts with the catalytic zinc; the Ser-2 side chain occupies the S1'-binding site and also forms a hydrogen bond to the carboxyl end of the catalytic Glu, whereas Leu-3 occupies the S2' recognition site. Penetration of the trunk region further than 5 residues into the substrate binding cleft appears to be prevented by the b-barrel, which itself interacts with the proteinase near its Met turn (19). Peptide mimetics of the trunk at concentrations up to about 100 mM do not inhibit the protease, demonstrating that the barrel is essential for inhibitory activity [, ].Structurally and functionally these inhibitors are closely related to the lipocalins, fatty acid-binding proteins, avidins and the enigmatic triabin.Together these five protein families constitute the calycin superfamily []. The proteins are characterised by their high specificity for small hydrophobic molecules and by their ability to form complexes with soluble macromolecules either through intramolecular disulphides or protein-protein interactions [].
