PDBsum entry 1hfc

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Metalloprotease PDB id
Protein chain
157 a.a. *
_ZN ×2
Waters ×88
* Residue conservation analysis
PDB id:
Name: Metalloprotease
Title: 1.56 angstrom structure of mature truncated human fibroblast collagenase
Structure: Fibroblast collagenase. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
1.50Å     R-factor:   0.174    
Authors: J.C.Spurlino,D.L.Smith
Key ref: J.C.Spurlino et al. (1994). 1.56 A structure of mature truncated human fibroblast collagenase. Proteins, 19, 98. PubMed id: 8090713
13-Sep-94     Release date:   26-Jan-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P03956  (MMP1_HUMAN) -  Interstitial collagenase
469 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Interstitial collagenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves preferentially one bond in native collagen. Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N-terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1' is a hydrophobic residue.
      Cofactor: Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular matrix   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     3 terms  


Proteins 19:98 (1994)
PubMed id: 8090713  
1.56 A structure of mature truncated human fibroblast collagenase.
J.C.Spurlino, A.M.Smallwood, D.D.Carlton, T.M.Banks, K.J.Vavra, J.S.Johnson, E.R.Cook, J.Falvo, R.C.Wahl, T.A.Pulvino.
The X-ray crystal structure of a 19 kDa active fragment of human fibroblast collagenase has been determined by the multiple isomorphous replacement method and refined at 1.56 A resolution to an R-factor of 17.4%. The current structure includes a bound hydroxamate inhibitor, 88 waters and three metal atoms (two zincs and a calcium). The overall topology of the enzyme, comprised of a five stranded beta-sheet and three alpha-helices, is similar to the thermolysin-like metalloproteinases. There are some important differences between the collagenase and thermolysin families of enzymes. The active site zinc ligands are all histidines (His-218, His-222, and His-228). The presence of a second zinc ion in a structural role is a unique feature of the matrix metalloproteinases. The binding properties of the active site cleft are more dependent on the main chain conformation of the enzyme (and substrate) compared with thermolysin. A mechanism of action for peptide cleavage similar to that of thermolysin is proposed for fibroblast collagenase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
16621578 S.Nakatani, M.Ikura, S.Yamamoto, Y.Nishita, S.Itadani, H.Habashita, T.Sugiura, K.Ogawa, H.Ohno, K.Takahashi, H.Nakai, and M.Toda (2006).
Design and synthesis of novel metalloproteinase inhibitors.
  Bioorg Med Chem, 14, 5402-5422.  
16374783 Y.J.Huang, R.Tejero, R.Powers, and G.T.Montelione (2006).
A topology-constrained distance network algorithm for protein structure determination from NOESY data.
  Proteins, 62, 587-603.  
15474975 A.Pardo, and M.Selman (2005).
MMP-1: the elder of the family.
  Int J Biochem Cell Biol, 37, 283-288.  
14679206 K.Conant, C.St Hillaire, H.Nagase, R.Visse, D.Gary, N.Haughey, C.Anderson, J.Turchan, and A.Nath (2004).
Matrix metalloproteinase 1 interacts with neuronal integrins and stimulates dephosphorylation of Akt.
  J Biol Chem, 279, 8056-8062.  
14532275 H.I.Park, Y.Jin, D.R.Hurst, C.A.Monroe, S.Lee, M.A.Schwartz, and Q.X.Sang (2003).
The intermediate S1' pocket of the endometase/matrilysin-2 active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling.
  J Biol Chem, 278, 51646-51653.  
12832766 V.Oganesyan, D.Busso, J.Brandsen, S.Chen, J.Jancarik, R.Kim, and S.H.Kim (2003).
Structure of the hypothetical protein AQ_1354 from Aquifex aeolicus.
  Acta Crystallogr D Biol Crystallogr, 59, 1219-1223.
PDB code: 1oz9
12887053 W.Bode, and K.Maskos (2003).
Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases.
  Biol Chem, 384, 863-872.  
12228918 J.L.Lauer-Fields, D.Juska, and G.B.Fields (2002).
Matrix metalloproteinases and collagen catabolism.
  Biopolymers, 66, 19-32.  
12437092 J.L.Lauer-Fields, and G.B.Fields (2002).
Triple-helical peptide analysis of collagenolytic protease activity.
  Biol Chem, 383, 1095-1105.  
11848217 T.Fujisawa, S.Odake, Y.Ogawa, J.Yasuda, Y.Morita, and T.Morikawa (2002).
Design and synthesis of sulfur based inhibitors of matrix metalloproteinase-1.
  Chem Pharm Bull (Tokyo), 50, 239-252.  
11592410 F.Grams, H.Brandstetter, S.D'Alò, D.Geppert, H.W.Krell, H.Leinert, V.Livi, E.Menta, A.Oliva, G.Zimmermann, F.Gram, H.Brandstetter, S.D'Alò, D.Geppert, H.W.Krell, H.Leinert, E.Livi VMenta, A.Oliva, and G.Zimmermann (2001).
Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors.
  Biol Chem, 382, 1277-1285.  
11248710 V.Knäuper, M.L.Patterson, F.X.Gomis-Rüth, B.Smith, A.Lyons, A.J.Docherty, and G.Murphy (2001).
The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivity.
  Eur J Biochem, 268, 1888-1896.  
10788434 J.L.Lauer-Fields, K.A.Tuzinski, K.Shimokawa, H.Nagase, and G.B.Fields (2000).
Hydrolysis of triple-helical collagen peptide models by matrix metalloproteinases.
  J Biol Chem, 275, 13282-13290.  
10662694 J.Ottl, D.Gabriel, G.Murphy, V.Knäuper, Y.Tominaga, H.Nagase, M.Kröger, H.Tschesche, W.Bode, and L.Moroder (2000).
Recognition and catabolism of synthetic heterotrimeric collagen peptides by matrix metalloproteinases.
  Chem Biol, 7, 119-132.  
10415719 B.De, M.G.Natchus, M.Cheng, S.Pikul, N.G.Almstead, Y.O.Taiwo, C.E.Snider, L.Chen, B.Barnett, F.Gu, and M.Dowty (1999).
The next generation of MMP inhibitors. Design and synthesis.
  Ann N Y Acad Sci, 878, 40-60.  
9888808 C.M.Holman, C.C.Kan, M.R.Gehring, and H.E.Van Wart (1999).
Role of His-224 in the anomalous pH dependence of human stromelysin-1.
  Biochemistry, 38, 677-681.  
10366106 G.N.Smith, E.A.Mickler, K.A.Hasty, and K.D.Brandt (1999).
Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme.
  Arthritis Rheum, 42, 1140-1146.  
10545322 K.Briknarová, A.Grishaev, L.Bányai, H.Tordai, L.Patthy, and M.Llinás (1999).
The second type II module from human matrix metalloproteinase 2: structure, function and dynamics.
  Structure, 7, 1235-1245.
PDB code: 1cxw
10455161 L.L.Johnson, D.A.Bornemeier, J.A.Janowicz, J.Chen, A.G.Pavlovsky, and D.F.Ortwine (1999).
Effect of species differences on stromelysin-1 (MMP-3) inhibitor potency. An explanation of inhibitor selectivity using homology modeling and chimeric proteins.
  J Biol Chem, 274, 24881-24887.  
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.
  Ann N Y Acad Sci, 878, 73-91.  
9446583 A.Mucha, P.Cuniasse, R.Kannan, F.Beau, A.Yiotakis, P.Basset, and V.Dive (1998).
Membrane type-1 matrix metalloprotease and stromelysin-3 cleave more efficiently synthetic substrates containing unusual amino acids in their P1' positions.
  J Biol Chem, 273, 2763-2768.  
  9792098 B.C.Finzel, E.T.Baldwin, G.L.Bryant, G.F.Hess, J.W.Wilks, C.M.Trepod, J.E.Mott, V.P.Marshall, G.L.Petzold, R.A.Poorman, T.J.O'Sullivan, H.J.Schostarez, and M.A.Mitchell (1998).
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.
  Protein Sci, 7, 2118-2126.
PDB codes: 1usn 2usn
  9827994 B.J.Stockman, D.J.Waldon, J.A.Gates, T.A.Scahill, D.A.Kloosterman, S.A.Mizsak, E.J.Jacobsen, K.L.Belonga, M.A.Mitchell, B.Mao, J.D.Petke, L.Goodman, E.A.Powers, S.R.Ledbetter, P.S.Kaytes, G.Vogeli, V.P.Marshall, G.L.Petzold, and R.A.Poorman (1998).
Solution structures of stromelysin complexed to thiadiazole inhibitors.
  Protein Sci, 7, 2281-2286.
PDB code: 3usn
  9655333 H.Brandstetter, R.A.Engh, E.G.Von Roedern, L.Moroder, R.Huber, W.Bode, and F.Grams (1998).
Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data.
  Protein Sci, 7, 1303-1309.
PDB codes: 1a85 1a86
  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.  
9154920 J.J.Perona, C.A.Tsu, C.S.Craik, and R.J.Fletterick (1997).
Crystal structure of an ecotin-collagenase complex suggests a model for recognition and cleavage of the collagen triple helix.
  Biochemistry, 36, 5381-5392.
PDB code: 1azz
8999811 Y.Zhang, W.L.Dean, and R.D.Gray (1997).
Cooperative binding of Ca2+ to human interstitial collagenase assessed by circular dichroism, fluorescence, and catalytic activity.
  J Biol Chem, 272, 1444-1447.  
8756473 A.R.Welch, C.M.Holman, M.Huber, M.C.Brenner, M.F.Browner, and H.E.Van Wart (1996).
Understanding the P1' specificity of the matrix metalloproteinases: effect of S1' pocket mutations in matrilysin and stromelysin-1.
  Biochemistry, 35, 10103-10109.  
8647077 B.Chevrier, H.D'Orchymont, C.Schalk, C.Tarnus, and D.Moras (1996).
The structure of the Aeromonas proteolytica aminopeptidase complexed with a hydroxamate inhibitor. Involvement in catalysis of Glu151 and two zinc ions of the co-catalytic unit.
  Eur J Biochem, 237, 393-398.
PDB code: 1igb
8639603 D.R.Wetmore, and K.D.Hardman (1996).
Roles of the propeptide and metal ions in the folding and stability of the catalytic domain of stromelysin (matrix metalloproteinase 3).
  Biochemistry, 35, 6549-6558.  
8765610 H.Nagase, and G.B.Fields (1996).
Human matrix metalloproteinase specificity studies using collagen sequence-based synthetic peptides.
  Biopolymers, 40, 399-416.  
8662603 L.Bányai, H.Tordai, and L.Patthty (1996).
Structure and domain-domain interactions of the gelatin binding site of human 72-kilodalton type IV collagenase (gelatinase A, matrix metalloproteinase 2).
  J Biol Chem, 271, 12003-12008.  
8917445 R.A.Williamson, D.Natalia, C.K.Gee, G.Murphy, M.D.Carr, and R.B.Freedman (1996).
Chemically and conformationally authentic active domain of human tissue inhibitor of metalloproteinases-2 refolded from bacterial inclusion bodies.
  Eur J Biochem, 241, 476-483.  
8888065 T.E.Cawston (1996).
Metalloproteinase inhibitors and the prevention of connective tissue breakdown.
  Pharmacol Ther, 70, 163-182.  
8836097 T.Fujii, Y.Hata, T.Wakagi, N.Tanaka, and T.Oshima (1996).
Novel zinc-binding centre in thermoacidophilic archaeal ferredoxins.
  Nat Struct Biol, 3, 834-837.
PDB code: 1xer
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.  
  9164646 W.D.Shingleton, D.J.Hodges, P.Brick, and T.E.Cawston (1996).
Collagenase: a key enzyme in collagen turnover.
  Biochem Cell Biol, 74, 759-775.  
8626483 Y.Zhang, and R.D.Gray (1996).
Characterization of folded, intermediate, and unfolded states of recombinant human interstitial collagenase.
  J Biol Chem, 271, 8015-8021.  
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
  8535233 J.W.Becker, A.I.Marcy, L.L.Rokosz, M.G.Axel, J.J.Burbaum, P.M.Fitzgerald, P.M.Cameron, C.K.Esser, W.K.Hagmann, and J.D.Hermes (1995).
Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme.
  Protein Sci, 4, 1966-1976.
PDB codes: 1slm 1sln
8527834 R.C.Jackson (1995).
Update on computer-aided drug design.
  Curr Opin Biotechnol, 6, 646-651.  
  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.
  Protein Sci, 4, 823-840.  
7583637 W.Stöcker, and W.Bode (1995).
Structural features of a superfamily of zinc-endopeptidases: the metzincins.
  Curr Opin Struct Biol, 5, 383-390.  
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.