Krueppel-like factor 5 (KLF5) belongs to the Kruppel family, whose members bind GC-rich DNA elements and activate or repress their target genes in a promoter context and/or cellular environment-dependent manner []. KLF5 is a zinc-finger transcription factor promoting cell proliferation, cell-cycle progression and survival []. It regulates transcription of a number of genes, such as the platelet-derived growth factor-alpha (PDGF-alpha), CyclinD1, Pim1 and PPARgamma []. It has been implicated in pathways critical to carcinogenesis [].
This entry represents the N-terminal substrate-binding domain of the Lon protease. This ATP-dependent enzyme, a serine peptidase belonging to the MEROPS peptidase family S16, is conserved in archaeal, bacterial and eukaryotic organisms and catalyses rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins. In eukaryotes, the majority of the proteins are located in the mitochondrial matrix [, ]. In yeast, Pim1, is located in the mitochondrial matrix and required for mitochondrial function. It is constitutively expressed but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response [].The structure of this domain has been determined and it represents a general protein and polypeptide interaction domain [, , , ].
This entry represents the N-terminal substrate-binding domain of the Lon protease. This ATP-dependent enzyme, a serine peptidase belonging to the MEROPS peptidase family S16, is conserved in archaeal, bacterial and eukaryotic organisms and catalyses rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins. In eukaryotes, the majority of the proteins are located in the mitochondrial matrix [, ]. In yeast, Pim1, is located in the mitochondrial matrix and required for mitochondrial function. It is constitutively expressed but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response [].The structure of this domain has been determined and it represents a general protein and polypeptide interaction domain [, , , ].
Lon protease belongs to the S16 peptidase family and is an ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins, as well as certain short-lived regulatory proteins. It is required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress []. In pathogenic bacteria, it is required for the expression of virulence genes that promote cell infection [].Lon (La) protease was the first ATP-dependent protease to be purified fromE. coli [, , , ]. The enzyme is a homotetramer of 87kDa subunits, with one proteolytic and one ATP-binding site per monomer, making it structurally less complex than other known ATP-dependent proteases []. Despite this relative structural simplicity, Lon recognises its substrates directly, without delegating the task of substrate recognition to other enzymes []. This signature defines the bacterial and eukaryotic lon proteases. This family of sequences does not include the archaeal lon homologues, . In the eukaryotes the majority of the proteins are located in the mitochondrial matrix [, ]. The yeast homologue, Pim1, is required for mitochondrial function and is constitutively expressed, but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response [].
The regulator of chromosome condensation (RCC1) []is a eukaryotic proteinwhich binds to chromatin and interacts with ran, a nuclear GTP-bindingprotein , to promote the loss of bound GDP and the uptake offresh GTP, thus acting as a guanine-nucleotide dissociation stimulator (GDS).The interaction of RCC1 with ran probably plays an important role in theregulation of gene expression.RCC1, known as PRP20 or SRM1 in yeast, pim1 in fission yeast and BJ1 inDrosophila, is a protein that contains seven tandem repeats of a domain ofabout 50 to 60 amino acids. As shown in the following schematicrepresentation, the repeats make up the major part of the length of theprotein. Outside the repeat region, there is just a small N-terminal domain ofabout 40 to 50 residues and, in the Drosophila protein only, a C-terminaldomain of about 130 residues.+----+-------+-------+-------+-------+-------+-------+-------+-------------+|N-t.|Rpt. 1 |Rpt. 2 |Rpt. 3 |Rpt. 4 |Rpt. 5 |Rpt. 6 |Rpt. 7 | C-terminal |+----+-------+-------+-------+-------+-------+-------+-------+-------------+The RCC1-type of repeat is also found in the X-linked retinitis pigmentosaGTPase regulator []. The RCC repeats form a β-propellerstructure.
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes []. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base []. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [, ].This signature defines the active site of the serine peptidases belonging to the MEROPS peptidase family S16 (lon protease family, clan SF). These proteases which are dependent on the hydrolysis of ATP for their activity and have a serine in their active site, they include:Bacterial ATP-dependent proteases [, ]. The prototype of those bacterial enzymes is the Escherichia coli La protease () (gene lon). La is capable of hydrolysing large proteins; it degrades short-lived regulatory (such as rcsA and sulA) and abnormal proteins. It is a cytoplasmic protein of 87kDa that associates as an homotetramer. Its proteolytic activity is stimulated by single-stranded DNA.Eukaryotic mitochondrial matrix proteases [, ]. The prototype of these enzymes is the yeast PIM1 protease. It is a mitochondrial matrix protein of 120kDa that associated as an homohexamer. It catalyses the initial step of mitochondrial protein degradation.Haemophilus influenzae lon-B (HI1324), a protein which does not contain the ATP-binding domain, but possess a slightly divergent form of the catalytic domain.
