CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [, , , ]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [, ]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [, , ]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [, ].
CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [, , , ]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [, ]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [, , ]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [, ].This entry represents a group of uncharacterised bacterial proteins containing a pair of CBS domains.
CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [, , , ]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [, ]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [, , ]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [, ].
This CBS domain is found associated with CorC_HlyC domain and/or CNNM domain, domains that are related to metal ion transport. This domain consists of a CBS pair which is thought to play a regulatory role, although its exact function is not clear. This domain is found in highly conserved proteins that either have unknown function or are predicted to be hemolysins, exotoxins involved in lysis of red blood cells in vitro [].
Plant CBSCBSPB proteins contain two cystathionine beta-synthase (CBS) domains and one PB1 domain. Arabidopsis contains 5 CBSCBSPBs. The presence of PB1domain along with a pair of CBS domains in a single protein suggests that these proteins might be involved in cellular signaling processes [].
CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [, , , ]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [, ]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [, , ]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [, ].This entry represents the CBS domain found in bacteria and plants proteins, including mitochondrial CBSX3 from Arabidopsis. CBSX3 interacts with and activates o-type thioredoxin (Trx-o2) Trx-o2, increasing its activity, which is known to play regulatory roles in the electron transport chain (ETC) complex II. This interaction regulates ROS generation in mitochondria and plays a key role in the modulation of plant development and growth [, ].
This domain can be found in a group of archaeal proteins that function as electron transfer proteins. They consist of a small (~35 amino acids) C- terminal metal-binding (MB) domain containing four cysteine residues arranged in a Cys-X(2)-Cys-X(14-19)-Cys-X(1-4)-Cys motif. The archaeal CBS proteins (ACP)-type MB domain can bind several metals, with iron and zinc being the most abundant metals [].The ACP-type MB domain consists of three short β-strands forming a compact anti-parallel β-sheet that packs against the CBS domains [].
This presumed domain is about 120 amino acids in length. It is found associated with CBS domains , as well as the CbiA domain . The function of this domain is unknown. It is named the DRTGG domain after some of the most conserved residues. This domain may be very distantly related to a pair of CBS domains. There are no significant sequence similarities, but its length and association with CBS domains supports this idea.
This entry represents the C-terminal region of Cystathionine beta-synthase (CBS), which includes two tandem repeats of the CBS domain. CBS is an hydro-lyase that catalyses the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine [, , ]. This protein is also involved in the production of hydrogen sulphide, a gasotransmitter with signalling and cytoprotective effects on neurons [, ]. CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [, , , ]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [, ]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [, , ]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [, ].
The Mg2+ transporter MgtE is an homodimeric transporter consisting of two cytosolic domains, the N-terminal domain and the CBS domain, and a C-terminal transmembrane domain with five membrane-spanning helices per monomer [].This domain is found at the N terminus of eubacterial magnesium transporters of the MgtE family . This domain is an intracellular domain that has an α-helical structure. The crystal structure of the MgtE transporter []shows two of 5 magnesium ions are in the interface between the N domain and the CBS domains. In the absence of magnesium there is a large shift between the N and CBS domains.
This domain is found at the N terminus of eubacterial magnesium transporters of the MgtE family . This domain is an intracellular domain that has an α-helical structure. The crystal structure of the MgtE transporter []shows two of 5 magnesium ions are in the interface between the N domain and the CBS domains. In the absence of magnesium there is a large shift between the N and CBS domains.
This small domain is found in a family of proteins with the CBS domain and two CBS domains with this domain found at the C terminus of the proteins, the domain is also found at the C terminus of some Na+/H+antiporters []. This domain is also found in CorC that is involved in Magnesium and cobalt efflux []. The function of this domain is uncertain but might be involved in modulating transport of ion substrates.
Members of this family closely resemble cysteine synthase but contain an additional C-terminal CBS domain. Cysteine synthase (O-acetylserine (thiol)-lyase) is the enzyme responsible for the formation of cysteine from O-acetyl-serine and hydrogen sulphide with the concomitant release of acetic acid - the function of many of these enzymes is unproven.This entry includes human CBS protein, which is a hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine [, , ]. Mutations in the CBS gene cause cystathionine beta-synthase deficiency (CBSD), an enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria [, ].
This is a family of closely related proteins with the phosphosugar-binding domain SIS (Sugar ISomerase) followed by two copies of the CBS (named after Cystathionine Beta Synthase) domain. The group includes GutQ, a protein of the glucitol operon [, ]and KpsF, a virulence factor involved in capsular polysialic acid biosynthesis in some pathogenic strains of Escherichia coli [].
This group represents an uncharacterised protein with a N-termial HtH domain and a C-terminal CBS domain pair. Proteins in this entry include transcriptional repressor CcpN from Bacillus subtilis. CcpN is a transcription repressor that binds to the promoter of gapB and pckA genes, preventing their expression. It acts as a regulator for catabolite repression of gluconeogenic genes [].
This domain is found associated with an N-terminal cyclic nucleotide-binding domain () and two CBS domains (). This domain, normally represents the C-terminal region, is uncharacterised; however, it seems to be similar to the nucleotidyltransferasedomain (), conserving the DXD motif, which strongly suggests that proteins containing this domain are also nucleotidyltransferases.
In Methanosarcina acetivorans, MA1821 is a L-aspartate semialdehyde sulfurtransferase required for O-acetylhomoserine sulfhydrylase (OAHS)-independent homocysteine (Hcy) biosynthesis [, ]. It contains two C-terminal cystathionine beta-synthase (CBS) domains. The CBS domains bind S-adenosyl-l-methionine (SAM) and 5'-methylthioadenosine (MTA), which induce a conformational change consistent with regulatory function. Another protein in the same pathway, MA1822, is involved in the reduction of the disulfide formed in MA1821 during the conversion of Asa (aspartate semialdehyde) to Hcy [, ].
This family of proteins restricted to the high GC Gram-positive bacteria includes GMP reductase from Mycobacterium smegmatis (GUAB1), which is involved in the purine-salvage pathway. This protein is composed of two domains: a catalytic domain with a TIM barrel structure and another that folds as a typical Bateman domain composed of two CBS domains (cystathionine-beta-synthase domain, CBS, ), which are essential for the NADPH-dependent conversion of GMP to IMP [].
Coilin is a nuclear phosphoprotein that concentrates within Cajal bodies (CBs) and has a role in small nuclear ribonucleoprotein (snRNP) biogenesis []. Coilin also acts to repress polymerase I activity in response to cisplatin-induced DNA damage, which could indicate a link between the DNA damage response and the inhibition of rRNA synthesis [].Conservation at the amino acid level is highest within coilin's N- and C-termini. The first N-terminal 92-amino acid domain have been shown to self-interact and to be essential for proper targeting of coilin to CBs [, ].
Synonym(s): Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase; Synonym(s): Guanosine 5'-monophosphate oxidoreductase This entry contains two related enzymes: IMP dehydrogenase and GMP reductase. These enzymes adopt a TIM barrel structure.IMP dehydrogenase () (IMPDH) catalyses the rate-limiting reaction of de novoGTP biosynthesis, the NAD-dependent reduction of IMP into XMP [].Inosine 5-phosphate + NAD++ H2O = xanthosine 5-phosphate + NADHIMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans []. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.GMP reductase () catalyses the irreversible and NADPH-dependent reductive deamination of GMP into IMP [].NADPH + guanosine 5-phosphate = NADP++ inosine 5-phosphate + NH3It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.
Synonym(s): Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase; Synonym(s): Guanosine 5'-monophosphate oxidoreductase This entry contains two related enzymes: IMP dehydrogenase and GMP reductase. These enzymes adopt a TIM barrel structure.IMP dehydrogenase () (IMPDH) catalyses the rate-limiting reaction of de novoGTP biosynthesis, the NAD-dependent reduction of IMP into XMP [].Inosine 5-phosphate + NAD++ H2O = xanthosine 5-phosphate + NADHIMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans []. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.GMP reductase () catalyses the irreversible and NADPH-dependent reductive deamination of GMP into IMP [].NADPH + guanosine 5-phosphate = NADP++ inosine 5-phosphate + NH3It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.
This presumed domain (used to be named as DUF39) is about is about 360 residues long. The function of this domain is not clear. It is found at N terminus in some proteins that have two C-terminal cystathionine beta-synthase (CBS) domains, such as MJ0100 from Methanocaldococcus jannaschii. This domain can also be found in proteins that contain two C-terminal inserted Fe4S domains []. In Methanocaldococcus jannaschii, MJ0100 (also known as MA1821) is involved in Hcy (homocysteine) biosynthesis. Its CBS domains bind S-adenosyl-l-methionine (SAM) and 5'-methylthioadenosine (MTA), which induce a conformational change consistent with regulatory function. Another protein in the homocysteine biosynthesis pathway, MA1822, is involved in the reduction of the disulfide formed in MA1821 during the conversion of Asa (aspartate semialdehyde) to Hcy [, ].The DUF39-CBS and DUF39-ferredoxin architectures repeatedly occur together in the genomes of methanogenic Archaea, suggesting they may be of diverged function. This is consistent with a phylogenetic reconstruction of the DUF39 family, which clearly distinguishes the CBS-associated and ferredoxin-associated DUF39s [].
Prokaryotic cells have a defence mechanism against a sudden heat-shock stress. Commonly, they induce a set of proteins that protect cellular proteins from being denatured by heat. Among such proteins are the GroE and DnaK chaperones whose transcription is regulated by a heat-shock repressor protein HrcA. HrcA is a winged helix-turn-helix repressor that negatively regulates the transcription of dnaK and groE operons by binding the upstream CIRCE (controlling inverted repeat of chaperone expression) element. In Bacillus subtilis this element is a perfect 9 base pair inverted repeat separated by a 9 base pair spacer. The crystal structure of a heat-inducible transcriptional repressor, HrcA, from Thermotoga maritima has been reported at 2.2A resolution. HrcA is composed of three domains: an N-terminal winged helix-turn-helix domain (WHTH), a GAF-like domain, and an inserted dimerizing domain (IDD). The IDD shows a unique structural fold with an anti-parallel β-sheet composed of three β-strands sided by four α-helices. HrcA crystallises as a dimer, which is formed through hydrophobic contact between the IDDs and a limited contact that involves conserved residues between the GAF-like domains []. The structural studies suggest that the inactive form of HrcA is the dimer and this is converted to its DNA-binding form by interaction with GroEL, which binds to a conserved C-terminal sequence region [, ]. Comparison of the HrcA-CIRCE complexes from B. subtilis and Bacillus thermoglucosidasius (Geobacillus thermoglucosidasius), which grow at vastly different ranges of temperature shows that the thermostability profiles were consistent with the difference in the growth temperatures suggesting that HrcA can function as a thermosensor to detect temperature changes in cells []. Any increase in temperature causes the dissociation of the HrcA from the CIRCE complex with the concomitant activation of transcription of the groE and dnaK operons. This domain represents the winged helix-turn-helix DNA-binding domain which is located close to the N terminus of HrcA. This domain is also found at the N terminus of a set of uncharacterised proteins that have two C-terminal CBS domains.
AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma []. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit [].AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer [, ]. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 [].The regulatory gamma subunit binds adenine nucleotides in the highly conserved nucleotide-binding domain consisting of four CBS motifs []. The gamma-1 subunit is the most abundant and shows wide tissue expression, as does gamma-2 whereas the gamma-3 isoform is almost exclusively expressed in skeletal muscle [].
AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma []. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit [].AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer [, ]. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 [].The regulatory gamma subunit binds adenine nucleotides in the highly conserved nucleotide-binding domain consisting of four CBS motifs []. The gamma-1 subunit is the most abundant and shows wide tissue expression, as does gamma-2 whereas the gamma-3 isoform is almost exclusively expressed in skeletal muscle [].
AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma []. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit [].AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer [, ]. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 [].The regulatory gamma subunit binds adenine nucleotides in the highly conserved nucleotide-binding domain consisting of four CBS motifs []. The gamma-1 subunit is the most abundant and shows wide tissue expression, as does gamma-2 whereas the gamma-3 isoform is almost exclusively expressed in skeletal muscle [].
