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Hydrolase(metalloproteinase) PDB id
1ast
Jmol
Contents
Protein chain
200 a.a. *
Metals
_ZN
Waters ×182
* Residue conservation analysis
PDB id:
1ast
Name: Hydrolase(metalloproteinase)
Title: Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases
Structure: Astacin. Chain: a. Engineered: yes
Source: Astacus astacus. Broad-fingered crayfish. Organism_taxid: 6715
Resolution:
1.80Å     R-factor:   0.158    
Authors: W.Bode,F.X.Gomis-Rueth,W.Stoecker
Key ref: W.Bode et al. (1992). Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases. Nature, 358, 164-167. PubMed id: 1319561 DOI: 10.1038/358164a0
Date:
21-Apr-93     Release date:   31-Jul-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07584  (ASTA_ASTFL) -  Astacin
Seq:
Struc:
251 a.a.
200 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.21  - Astacin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of peptide bonds in substrates containing five or more amino acids, preferentially with Ala in P1', and Pro in P2'.
      Cofactor: Zinc
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     3 terms  

 

 
DOI no: 10.1038/358164a0 Nature 358:164-167 (1992)
PubMed id: 1319561  
 
 
Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases.
W.Bode, F.X.Gomis-Rüth, R.Huber, R.Zwilling, W.Stöcker.
 
  ABSTRACT  
 
Astacin, a digestive zinc-endopeptidase from the crayfish Astacus astacus L., is the prototype for the 'astacin family', which includes mammalian metallo-endopeptidases and developmentally regulated proteins of man, fruitfly, frog and sea urchin. Here we report the X-ray crystal structure of astacin, which reveals a deep active-site cleft, with the zinc at its bottom ligated by three histidines, a water molecule and a more remote tyrosine. The third histidine (His 102) forms part of a consensus sequence, shared not only by the members of the astacin family, but also by otherwise sequentially unrelated proteinases, such as vertebrate collagenases. It may therefore represent the elusive 'third' zinc ligand in these enzymes. The amino terminus of astacin is buried forming an internal salt-bridge with Glu 103, adjacent to His 102. Astacin pro-forms extended at the N terminus, as observed for some 'latent' mammalian astacin homologues, did not exhibit this 'active' conformation, indicating an activation mechanism reminiscent of trypsin-like serine proteinases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding.
  J Biol Chem, 278, 25982-25989.
PDB code: 1uap
14653817 F.Möhrlen, H.Hutter, and R.Zwilling (2003).
The astacin protein family in Caenorhabditis elegans.
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12888571 J.P.Villa, G.P.Bertenshaw, and J.S.Bond (2003).
Critical amino acids in the active site of meprin metalloproteinases for substrate and peptide bond specificity.
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Probing the role of divalent metal ions in a bacterial psychrophilic metalloprotease: binding studies of an enzyme in the crystalline state by x-ray crystallography.
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PDB codes: 1o0q 1o0t 1om6 1om7 1om8 1omj
12437102 B.A.Doll, J.P.Villa, F.T.Ishmael, and J.S.Bond (2002).
Zinc ligands in an astacin family metalloprotease meprin A.
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11847292 J.Pei, and N.V.Grishin (2002).
Breaking the singleton of germination protease.
  Protein Sci, 11, 691-697.  
12077431 K.F.Huang, S.H.Chiou, T.P.Ko, J.M.Yuann, and A.H.Wang (2002).
The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium.
  Acta Crystallogr D Biol Crystallogr, 58, 1118-1128.
PDB code: 1kuf
12189145 S.Rösmann, D.Hahn, D.Lottaz, M.N.Kruse, W.Stöcker, and E.E.Sterchi (2002).
Activation of human meprin-alpha in a cell culture model of colorectal cancer is triggered by the plasminogen-activating system.
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11489172 A.Hallmann, P.Amon, K.Godl, M.Heitzer, and M.Sumper (2001).
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  Acta Crystallogr D Biol Crystallogr, 57, 361-368.
PDB codes: 1g12 1ge5 1ge6 1ge7
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Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.
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10387075 K.Fukasawa, K.M.Fukasawa, H.Iwamoto, J.Hirose, and M.Harada (1999).
The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme.
  Biochemistry, 38, 8299-8303.  
10415721 W.Bode, C.Fernandez-Catalan, F.Grams, F.X.Gomis-Rüth, H.Nagase, H.Tschesche, and K.Maskos (1999).
Insights into MMP-TIMP interactions.
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Structure of acutolysin-C, a haemorrhagic toxin from the venom of Agkistrodon acutus, providing further evidence for the mechanism of the pH-dependent proteolytic reaction of zinc metalloproteinases.
  Acta Crystallogr D Biol Crystallogr, 55, 1834-1841.
PDB code: 1qua
9746536 C.Meneghini, and S.Morante (1998).
The active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.
  Biophys J, 75, 1953-1963.  
  9739094 E.Schlagenhauf, R.Etges, and P.Metcalf (1998).
The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).
  Structure, 6, 1035-1046.
PDB code: 1lml
  9653544 H.H.Thorp (1998).
Bioinorganic chemistry and drug design: here comes zinc again.
  Chem Biol, 5, R125-R127.  
  10082367 I.L.Alberts, K.Nadassy, and S.J.Wodak (1998).
Analysis of zinc binding sites in protein crystal structures.
  Protein Sci, 7, 1700-1716.  
9013548 A.Chestukhin, L.Litovchick, K.Muradov, M.Batkin, and S.Shaltiel (1997).
Unveiling the substrate specificity of meprin beta on the basis of the site in protein kinase A cleaved by the kinase splitting membranal proteinase.
  J Biol Chem, 272, 3153-3160.  
9153232 C.H.Hung, H.R.Huang, C.J.Huang, F.L.Huang, and G.D.Chang (1997).
Purification and cloning of carp nephrosin, a secreted zinc endopeptidase of the astacin family.
  J Biol Chem, 272, 13772-13778.  
9346968 G.D.Johnson, and J.S.Bond (1997).
Activation mechanism of meprins, members of the astacin metalloendopeptidase family.
  J Biol Chem, 272, 28126-28132.  
8995407 M.L.Brader, N.C.Kaarsholm, S.E.Harnung, and M.F.Dunn (1997).
Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A magnetic circular dichroism study of the Co(II)-substituted insulin hexamer.
  J Biol Chem, 272, 1088-1094.  
9228090 S.Lee, D.E.Solow-Cordero, E.Kessler, K.Takahara, and D.S.Greenspan (1997).
Transforming growth factor-beta regulation of bone morphogenetic protein-1/procollagen C-proteinase and related proteins in fibrogenic cells and keratinocytes.
  J Biol Chem, 272, 19059-19066.  
9374478 T.Nonaka, N.Dohmae, Y.Hashimoto, and K.Takio (1997).
Amino acid sequences of metalloendopeptidases specific for acyl-lysine bonds from Grifola frondosa and Pleurotus ostreatus fruiting bodies.
  J Biol Chem, 272, 30032-30039.  
  9385650 V.Villeret, J.P.Chessa, C.Gerday, and J.Van Beeumen (1997).
Preliminary crystal structure determination of the alkaline protease from the Antarctic psychrophile Pseudomonas aeruginosa.
  Protein Sci, 6, 2462-2464.  
8612079 A.Cleasby, A.Wonacott, T.Skarzynski, R.E.Hubbard, G.J.Davies, A.E.Proudfoot, A.R.Bernard, M.A.Payton, and T.N.Wells (1996).
The x-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 angstrom resolution.
  Nat Struct Biol, 3, 470-479.
PDB code: 1pmi
8756323 F.Grams, V.Dive, A.Yiotakis, I.Yiallouros, S.Vassiliou, R.Zwilling, W.Bode, and W.Stöcker (1996).
Structure of astacin with a transition-state analogue inhibitor.
  Nat Struct Biol, 3, 671-675.
PDB codes: 1qji 1qjj
8798668 P.Marchand, M.Volkmann, and J.S.Bond (1996).
Cysteine mutations in the MAM domain result in monomeric meprin and alter stability and activity of the proteinase.
  J Biol Chem, 271, 24236-24241.  
8654408 S.Morante, L.Furenlid, G.Schiavo, F.Tonello, R.Zwilling, and C.Montecucco (1996).
X-ray absorption spectroscopy study of zinc coordination in tetanus neurotoxin, astacin, alkaline protease and thermolysin.
  Eur J Biochem, 235, 606-612.  
  8740360 V.Dhanaraj, Q.Z.Ye, L.L.Johnson, D.J.Hupe, D.F.Ortwine, J.B.Dunbar, J.R.Rubin, A.Pavlovsky, C.Humblet, and T.L.Blundell (1996).
X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
  Structure, 4, 375-386.  
7622493 A.Beaumont, M.J.O'Donohue, N.Paredes, N.Rousselet, M.Assicot, C.Bohuon, M.C.Fournié-Zaluski, and B.P.Roques (1995).
The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study.
  J Biol Chem, 270, 16803-16808.  
  8536976 A.L.Finelli, T.Xie, C.A.Bossie, R.K.Blackman, and R.W.Padgett (1995).
The tolkin gene is a tolloid/BMP-1 homologue that is essential for Drosophila development.
  Genetics, 141, 271-281.  
8771234 C.Montecucco, and G.Schiavo (1995).
Structure and function of tetanus and botulinum neurotoxins.
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8561847 D.Soler, T.Nomizu, W.E.Brown, Y.Shibata, and D.S.Auld (1995).
Matrilysin: expression, purification, and characterization.
  J Protein Chem, 14, 511-520.  
7737183 F.Grams, P.Reinemer, J.C.Powers, T.Kleine, M.Pieper, H.Tschesche, R.Huber, and W.Bode (1995).
X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design.
  Eur J Biochem, 228, 830-841.
PDB codes: 1jao 1jaq
  7883008 H.Ostolaza, A.Soloaga, and F.M.Goñi (1995).
The binding of divalent cations to Escherichia coli alpha-haemolysin.
  Eur J Biochem, 228, 39-44.  
7703375 H.Zaima, N.Ueyama, H.Adachi, and A.Nakamura (1995).
1H-, 13C-, and 113Cd-NMR study of the Cd(II) complex of a blocked peptide, Z-Cys-Ala-Pro-His-OMe, in organic solvents.
  Biopolymers, 35, 319-329.  
  7670368 J.S.Bond, and R.J.Beynon (1995).
The astacin family of metalloendopeptidases.
  Protein Sci, 4, 1247-1261.  
  8676727 M.J.Halpern (1995).
Lipids and atherosclerosis.
  Mol Aspects Med, 16, 509-710.  
7581298 O.Rossetto, F.Deloye, B.Poulain, R.Pellizzari, G.Schiavo, and C.Montecucco (1995).
The metallo-proteinase activity of tetanus and botulism neurotoxins.
  J Physiol Paris, 89, 43-50.  
7588817 S.Harada, T.Kinoshita, N.Kasai, S.Tsunasawa, and F.Sakiyama (1995).
Complete amino acid sequence of a zinc metalloendoprotease from Streptomyces caespitosus.
  Eur J Biochem, 233, 683-686.  
  8580839 S.R.Van Doren, A.V.Kurochkin, W.Hu, Q.Z.Ye, L.L.Johnson, D.J.Hupe, and E.R.Zuiderweg (1995).
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.
  Protein Sci, 4, 2487-2498.
PDB codes: 1ums 1umt
8561849 T.Pourmotabbed, J.A.Aelion, D.Tyrrell, K.A.Hasty, C.H.Bu, and C.L.Mainardi (1995).
Role of the conserved histidine and aspartic acid residues in activity and stabilization of human gelatinase B: an example of matrix metalloproteinases.
  J Protein Chem, 14, 527-535.  
  7663339 W.Stöcker, F.Grams, U.Baumann, P.Reinemer, F.X.Gomis-Rüth, D.B.McKay, and W.Bode (1995).
The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.
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7583637 W.Stöcker, and W.Bode (1995).
Structural features of a superfamily of zinc-endopeptidases: the metzincins.
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7978813 B.Lovejoy, A.Cleasby, A.M.Hassell, M.A.Luther, D.Weigl, G.McGeehan, M.H.Lambert, and S.R.Jordan (1994).
Structural analysis of the catalytic domain of human fibroblast collagenase.
  Ann N Y Acad Sci, 732, 375-378.  
  8069228 E.E.Hodgkin, I.C.Gillman, and R.J.Gilbert (1994).
Retrospective analysis of a secondary structure prediction: the catalytic domain of matrix metalloproteinases.
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7786341 G.Schiavo, O.Rossetto, F.Benfenati, B.Poulain, and C.Montecucco (1994).
Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus.
  Ann N Y Acad Sci, 710, 65-75.  
  7972338 J.B.Bjarnason, and J.W.Fox (1994).
Hemorrhagic metalloproteinases from snake venoms.
  Pharmacol Ther, 62, 325-372.  
7925363 M.J.Paine, A.M.Moura-da-Silva, R.D.Theakston, and J.M.Crampton (1994).
Cloning of metalloprotease genes in the carpet viper (Echis pyramidum leakeyi). Further members of the metalloprotease/disintegrin gene family.
  Eur J Biochem, 224, 483-488.  
7656013 N.Borkakoti, F.K.Winkler, D.H.Williams, A.D'Arcy, M.J.Broadhurst, P.A.Brown, W.H.Johnson, and E.J.Murray (1994).
Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.
  Nat Struct Biol, 1, 106-110.
PDB code: 2tcl
7656014 P.R.Gooley, J.F.O'Connell, A.I.Marcy, G.C.Cuca, S.P.Salowe, B.L.Bush, J.D.Hermes, C.K.Esser, W.K.Hagmann, and J.P.Springer (1994).
The NMR structure of the inhibited catalytic domain of human stromelysin-1.
  Nat Struct Biol, 1, 111-118.
PDB codes: 1srt 2srt
7656018 T.L.Blundell (1994).
Metalloproteinase superfamilies and drug design.
  Nat Struct Biol, 1, 73-75.  
  8137810 W.Bode, P.Reinemer, R.Huber, T.Kleine, S.Schnierer, and H.Tschesche (1994).
The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity.
  EMBO J, 13, 1263-1269.
PDB code: 1jap
8464881 B.L.Vallee, and D.S.Auld (1993).
Cocatalytic zinc motifs in enzyme catalysis.
  Proc Natl Acad Sci U S A, 90, 2715-2718.  
7901925 C.Montecucco, and G.Schiavo (1993).
Tetanus and botulism neurotoxins: a new group of zinc proteases.
  Trends Biochem Sci, 18, 324-327.  
  8223430 F.X.Gomis-Rüth, L.F.Kress, and W.Bode (1993).
First structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases.
  EMBO J, 12, 4151-4157.
PDB code: 1iag
  8143134 G.Schiavo, B.Poulain, F.Benfenati, B.R.DasGupta, and C.Montecucco (1993).
Novel targets and catalytic activities of bacterial protein toxins.
  Trends Microbiol, 1, 170-174.  
8248170 T.G.Wolfsberg, J.F.Bazan, C.P.Blobel, D.G.Myles, P.Primakoff, and J.M.White (1993).
The precursor region of a protein active in sperm-egg fusion contains a metalloprotease and a disintegrin domain: structural, functional, and evolutionary implications.
  Proc Natl Acad Sci U S A, 90, 10783-10787.  
  8253063 U.Baumann, S.Wu, K.M.Flaherty, and D.B.McKay (1993).
Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two-domain protein with a calcium binding parallel beta roll motif.
  EMBO J, 12, 3357-3364.
PDB code: 1kap
8508794 W.Stöcker, F.X.Gomis-Rüth, W.Bode, and R.Zwilling (1993).
Implications of the three-dimensional structure of astacin for the structure and function of the astacin family of zinc-endopeptidases.
  Eur J Biochem, 214, 215-231.
PDB code: 1iaf
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.