The Kazal domain is an evolutionary conserved protein domain usually indicative of serine proteaseinhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors.
In animals, serine protease inhibitors that act via their Kazal domain are grouped under the MEROPS inhibitor family I1, clan IA.[1][2]
Kazal 1edit
Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulfide bonds. Alignment also includes a single domain from transporters in the OATP/PGT family P46721.
Peptideproteinase inhibitors can be found as single domainproteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalyticcleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.
This family of Kazal inhibitors, belongs to MEROPS inhibitor family I1, clan IA. They inhibitserine peptidases of the S1 family (INTERPRO).[3] The members are primarily metazoan, but includes exceptions in the alveolata (apicomplexa), stramenopiles, higher plants and bacteria.
Kazal inhibitors, which inhibit a number of serine proteases (such as trypsin and elastase), belong to family of proteins that includes pancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor; and elastase inhibitor. These proteins contain between 1 and 7 Kazal-type inhibitor repeats.[4][5]
The structure of the Kazal repeat includes a large quantity of extended chain, 2 short alpha-helices and a 3-stranded anti-parallel beta sheet.[4] The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable.[5] Altering the enzyme-contact residues, and especially that of the active site bond, affects the strength of inhibition and specificity of the inhibitor for particular serine proteases.[5][6] The presence of this Pfam domain is usually indicative of serine protease inhibitors, however, Kazal-like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors.
^Rawlings ND, Tolle DP, Barrett AJ (March 2004). "Evolutionary families of peptidase inhibitors". Biochem. J. 378 (Pt 3): 705–16. doi:10.1042/BJ20031825. PMC1224039. PMID 14705960.
^ abWilliamson MP; Marion D; Wüthrich K (March 1984). "Secondary structure in the solution conformation of the proteinase inhibitor IIA from bull seminal plasma by nuclear magnetic resonance". J. Mol. Biol. 173 (3): 341–59. doi:10.1016/0022-2836(84)90125-6. PMID 6699915.
^ abcLaskowski M, Kato I, Ardelt W, Cook J, Denton A, Empie MW, Kohr WJ, Park SJ, Parks K, Schatzley BL (January 1987). "Ovomucoid third domains from 100 avian species: isolation, sequences, and hypervariability of enzyme-inhibitor contact residues". Biochemistry. 26 (1): 202–21. doi:10.1021/bi00375a028. PMID 3828298.
^Empie MW, Laskowski M (May 1982). "Thermodynamics and kinetics of single residue replacements in avian ovomucoid third domains: effect on inhibitor interactions with serine proteinases". Biochemistry. 21 (10): 2274–84. doi:10.1021/bi00539a002. PMID 7046785.
^Schlott B, Wöhnert J, Icke C, Hartmann M, Ramachandran R, Gührs KH, Glusa E, Flemming J, Görlach M, Grosse F, Ohlenschläger O (April 2002). "Interaction of Kazal-type inhibitor domains with serine proteinases: biochemical and structural studies". J. Mol. Biol. 318 (2): 533–46. doi:10.1016/S0022-2836(02)00014-1. PMID 12051857.
^Stubbs MT, Morenweiser R, Stürzebecher J, Bauer M, Bode W, Huber R, Piechottka GP, Matschiner G, Sommerhoff CP, Fritz H, Auerswald EA (August 1997). "The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition". J. Biol. Chem. 272 (32): 19931–7. doi:10.1074/jbc.272.32.19931. PMID 9242660.
^van de Locht A, Lamba D, Bauer M, Huber R, Friedrich T, Kröger B, Höffken W, Bode W (November 1995). "Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin". EMBO J. 14 (21): 5149–57. doi:10.1002/j.1460-2075.1995.tb00199.x. PMC394622. PMID 7489704.
This article incorporates text from the public domain Pfam and InterPro: IPR002350
This article incorporates text from the public domain Pfam and InterPro: IPR011497
April 18, 2024
kazal, domain, evolutionary, conserved, protein, domain, usually, indicative, serine, protease, inhibitors, however, kazal, like, domains, also, seen, extracellular, part, agrins, which, known, protease, inhibitors, kazal, type, serine, protease, inhibitor, do. The Kazal domain is an evolutionary conserved protein domain usually indicative of serine protease inhibitors However kazal like domains are also seen in the extracellular part of agrins which are not known to be protease inhibitors Kazal type serine protease inhibitor domainthe structure of the follistatin activin complexIdentifiersSymbolKazal 1PfamPF00050InterProIPR002350PROSITEPDOC00254SCOP23sgb SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryKazal type serine protease inhibitor domainstructure of fs1 the heparin binding domain of follistatinIdentifiersSymbolKazal 2PfamPF07648InterProIPR011497PROSITEPDOC00254SCOP23sgb SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryIn animals serine protease inhibitors that act via their Kazal domain are grouped under the MEROPS inhibitor family I1 clan IA 1 2 Kazal 1 editKazal domains often occur in tandem arrays Small alpha beta fold containing three disulfide bonds Alignment also includes a single domain from transporters in the OATP PGT family P46721 Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins these are referred to as either simple or compound inhibitors respectively In many cases they are synthesised as part of a larger precursor protein either as a prepropeptide or as an N terminal domain associated with an inactive peptidase or zymogen This domain prevents access of the substrate to the active site Removal of the N terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism while yet others use a conformational change based trapping mechanism that depends on their structural and thermodynamic properties This family of Kazal inhibitors belongs to MEROPS inhibitor family I1 clan IA They inhibit serine peptidases of the S1 family INTERPRO 3 The members are primarily metazoan but includes exceptions in the alveolata apicomplexa stramenopiles higher plants and bacteria Kazal inhibitors which inhibit a number of serine proteases such as trypsin and elastase belong to family of proteins that includes pancreatic secretory trypsin inhibitor avian ovomucoid acrosin inhibitor and elastase inhibitor These proteins contain between 1 and 7 Kazal type inhibitor repeats 4 5 The structure of the Kazal repeat includes a large quantity of extended chain 2 short alpha helices and a 3 stranded anti parallel beta sheet 4 The inhibitor makes 11 contacts with its enzyme substrate unusually 8 of these important residues are hypervariable 5 Altering the enzyme contact residues and especially that of the active site bond affects the strength of inhibition and specificity of the inhibitor for particular serine proteases 5 6 The presence of this Pfam domain is usually indicative of serine protease inhibitors however Kazal like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors Human proteins with Kazal 1 domains AGRIN CPAMD8 FST FSTL3 FSTL4 FSTL5 IGFBPL1 SMOC1 SPARC SPARCL1 SPINK1 SPINK2 SPINK4 SPINK5 SPINK5L2 SPINK5L3 SPINK6 SPINK7 SPINK9 TMEFF1 TMEFF2Kazal 2 editThis domain is usually indicative of serine protease inhibitors that belong to Merops inhibitor families I1 I2 I17 and I31 However kazal like domains are also seen in the extracellular part of agrins which are not known to be protease inhibitors Kazal domains often occur in tandem arrays and have a central alpha helix a short two stranded antiparallel beta sheet and several disulphide bonds 7 8 9 The amino terminal segment of this domain binds to the active site of its target proteases thus inhibiting their function Human proteins with Kazal 2 domains C6 CFI FSTL1 FSTL3 HTRA1 HTRA3 HTRA4 IGFBP7 KAZALD1 LST3 RECK SLC21A8 SLCO1A2 SLCO1B1 SLCO1B3 SLCO1C1 SLCO2A1 SLCO3A1 SLCO4A1 SLCO4C1 SLCO5A1 SLCO6A1 SMOC2 SPINK5 SPOCK1 SPOCK2 SPOCK3 WFIKKN1 WFIKKN2References edit MEROPS family I1 InterPro IPR001239 Rawlings ND Tolle DP Barrett AJ March 2004 Evolutionary families of peptidase inhibitors Biochem J 378 Pt 3 705 16 doi 10 1042 BJ20031825 PMC 1224039 PMID 14705960 a b Williamson MP Marion D Wuthrich K March 1984 Secondary structure in the solution conformation of the proteinase inhibitor IIA from bull seminal plasma by nuclear magnetic resonance J Mol Biol 173 3 341 59 doi 10 1016 0022 2836 84 90125 6 PMID 6699915 a b c Laskowski M Kato I Ardelt W Cook J Denton A Empie MW Kohr WJ Park SJ Parks K Schatzley BL January 1987 Ovomucoid third domains from 100 avian species isolation sequences and hypervariability of enzyme inhibitor contact residues Biochemistry 26 1 202 21 doi 10 1021 bi00375a028 PMID 3828298 Empie MW Laskowski M May 1982 Thermodynamics and kinetics of single residue replacements in avian ovomucoid third domains effect on inhibitor interactions with serine proteinases Biochemistry 21 10 2274 84 doi 10 1021 bi00539a002 PMID 7046785 Schlott B Wohnert J Icke C Hartmann M Ramachandran R Guhrs KH Glusa E Flemming J Gorlach M Grosse F Ohlenschlager O April 2002 Interaction of Kazal type inhibitor domains with serine proteinases biochemical and structural studies J Mol Biol 318 2 533 46 doi 10 1016 S0022 2836 02 00014 1 PMID 12051857 Stubbs MT Morenweiser R Sturzebecher J Bauer M Bode W Huber R Piechottka GP Matschiner G Sommerhoff CP Fritz H Auerswald EA August 1997 The three dimensional structure of recombinant leech derived tryptase inhibitor in complex with trypsin Implications for the structure of human mast cell tryptase and its inhibition J Biol Chem 272 32 19931 7 doi 10 1074 jbc 272 32 19931 PMID 9242660 van de Locht A Lamba D Bauer M Huber R Friedrich T Kroger B Hoffken W Bode W November 1995 Two heads are better than one crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin EMBO J 14 21 5149 57 doi 10 1002 j 1460 2075 1995 tb00199 x PMC 394622 PMID 7489704 This article incorporates text from the public domain Pfam and InterPro IPR002350 This article incorporates text from the public domain Pfam and InterPro IPR011497 Retrieved from https en wikipedia org w index php title Kazal domain amp oldid 994609904, wikipedia, wiki, book, books, library,
