PDBsum entry 1cgf

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Hydrolase (metalloprotease) PDB id
Protein chain
162 a.a. *
_CA ×6
_ZN ×4
Waters ×543
* Residue conservation analysis
PDB id:
Name: Hydrolase (metalloprotease)
Title: Crystal structures of recombinant 19-kda human fibroblast collagenase complexed to itself
Structure: Fibroblast collagenase. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdna
2.10Å     R-factor:   0.197    
Authors: B.Lovejoy,A.M.Hassell,M.A.Luther,D.Weigl,S.R.Jordan
Key ref:
B.Lovejoy et al. (1994). Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself. Biochemistry, 33, 8207-8217. PubMed id: 8031754 DOI: 10.1021/bi00193a006
03-Feb-94     Release date:   31-Mar-95    
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Protein chains
Pfam   ArchSchema ?
P03956  (MMP1_HUMAN) -  Interstitial collagenase
469 a.a.
162 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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  


DOI no: 10.1021/bi00193a006 Biochemistry 33:8207-8217 (1994)
PubMed id: 8031754  
Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself.
B.Lovejoy, A.M.Hassell, M.A.Luther, D.Weigl, S.R.Jordan.
Collagenase is a member of the matrix metalloproteinase (MMP) family of enzymes. Aberrant regulation of this family has been implicated in pathologies such as arthritis and metastasis. Two crystal forms of the catalytic (19-kDa) domain of human fibroblast collagenase have been determined using collagenase complexed with a peptide-based inhibitor (CPLX) as a starting model [Lovejoy et al. (1994) Science 263, 375]. The first crystal form (CF1) contains one molecule in the asymmetric unit and has been determined at 1.9-A resolution with an R factor of 19.8%. The second crystal form (CF2) contains two molecules (A and B) in the asymmetric unit and has been determined at 2.1-A resolution with an R factor of 19.7%. The catalytic domain of collagenase is spherical with an active site cleft that contains a ligated catalytic zinc ion. Collagenase shares some structural homology with the bacterial zinc proteinase, thermolysin [Matthews et al. (1972) Nature, New Biol. 238, 37], and the crayfish digestive peptidase, astacin [Bode et al. (1992) Nature 358, 164]. The amino terminus (Leu 102 to Gly 105) of CF1 and CF2 molecules A and B differs from the conformation found in CPLX by bending away from the molecule and interacting with the active site cleft of symmetry-related molecules. In this alternative conformation, both the mainchain nitrogen and carbonyl oxygen of Leu 102 ligate the symmetry-related catalytic zinc. Although there are structural differences in the active site clefts of CF1, CF2, and CPLX, a number of complex-stabilizing interactions are conserved. The structure of collagenase will be useful for developing compounds that selectively inhibit individual members of the closely related matrix metalloproteinase family.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19609998 I.Bertini, M.Fragai, C.Luchinat, M.Melikian, and C.Venturi (2009).
Characterisation of the MMP-12-elastin adduct.
  Chemistry, 15, 7842-7845.  
18451556 H.Kobayashi, N.Morisaki, H.Miyachi, and Y.Hashimoto (2008).
Coordination of divalent metal cation to amide group to form adduct ion in FAB mass spectrometry: implication of Zn2+ in enzymatic hydrolysis of amide bond.
  Chem Pharm Bull (Tokyo), 56, 672-676.  
17710450 L.A.Alcaraz, L.Banci, I.Bertini, F.Cantini, A.Donaire, and L.Gonnelli (2007).
Matrix metalloproteinase-inhibitor interaction: the solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors.
  J Biol Inorg Chem, 12, 1197-1206.
PDB codes: 2jnp 2jt5 2jt6
17997411 R.Bhaskaran, M.O.Palmier, N.A.Bagegni, X.Liang, and S.R.Van Doren (2007).
Solution structure of inhibitor-free human metalloelastase (MMP-12) indicates an internal conformational adjustment.
  J Mol Biol, 374, 1333-1344.
PDB code: 2poj
16699182 D.E.Danley (2006).
Crystallization to obtain protein-ligand complexes for structure-aided drug design.
  Acta Crystallogr D Biol Crystallogr, 62, 569-575.  
17096442 I.Bertini, V.Calderone, M.Fragai, C.Luchinat, M.Maletta, and K.J.Yeo (2006).
Snapshots of the reaction mechanism of matrix metalloproteinases.
  Angew Chem Int Ed Engl, 45, 7952-7955.
PDB codes: 2oxu 2oxw 2oxz 2oy2 2oy4
16890240 S.Iyer, R.Visse, H.Nagase, and K.R.Acharya (2006).
Crystal structure of an active form of human MMP-1.
  J Mol Biol, 362, 78-88.
PDB code: 2clt
16320288 G.Grasso, R.D'Agata, E.Rizzarelli, G.Spoto, L.D'Andrea, C.Pedone, A.Picardi, A.Romanelli, M.Fragai, and K.J.Yeo (2005).
Activity of anchored human matrix metalloproteinase-1 catalytic domain on Au (111) surfaces monitored by ESI-MS.
  J Mass Spectrom, 40, 1565-1571.  
15036267 F.Augé, W.Hornebeck, and J.Y.Laronze (2004).
A novel strategy for designing specific gelatinase A inhibitors: potential use to control tumor progression.
  Crit Rev Oncol Hematol, 49, 277-282.  
14709555 P.L.Tsai, C.H.Chen, C.J.Huang, C.M.Chou, and G.D.Chang (2004).
Purification and cloning of an endogenous protein inhibitor of carp nephrosin, an astacin metalloproteinase.
  J Biol Chem, 279, 11146-11155.  
14500885 L.Watanabe, J.D.Shannon, R.H.Valente, A.Rucavado, A.Alape-Girón, A.S.Kamiguti, R.D.Theakston, J.W.Fox, J.M.Gutiérrez, and R.K.Arni (2003).
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities.
  Protein Sci, 12, 2273-2281.
PDB code: 1nd1
  10422833 A.G.Pavlovsky, M.G.Williams, Q.Z.Ye, D.F.Ortwine, C.F.Purchase, A.D.White, V.Dhanaraj, B.D.Roth, L.L.Johnson, D.Hupe, C.Humblet, and T.L.Blundell (1999).
X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity.
  Protein Sci, 8, 1455-1462.
PDB codes: 1b8y 1caq 1ciz 1qia 1qic
10353819 F.J.Moy, P.K.Chanda, J.M.Chen, S.Cosmi, W.Edris, J.S.Skotnicki, J.Wilhelm, and R.Powers (1999).
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
  Biochemistry, 38, 7085-7096.
PDB codes: 3ayk 4ayk
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.  
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
9417124 B.P.Mari, I.C.Anderson, S.E.Mari, Y.Ning, Y.Lutz, L.Kobzik, and M.A.Shipp (1998).
Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism.
  J Biol Chem, 273, 618-626.  
9484219 F.J.Moy, P.K.Chanda, S.Cosmi, M.R.Pisano, C.Urbano, J.Wilhelm, and R.Powers (1998).
High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR.
  Biochemistry, 37, 1495-1504.
PDB codes: 1ayk 2ayk
  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.  
9724722 Y.H.Ding, K.Javaherian, K.M.Lo, R.Chopra, T.Boehm, J.Lanciotti, B.A.Harris, Y.Li, R.Shapiro, E.Hohenester, R.Timpl, J.Folkman, and D.C.Wiley (1998).
Zinc-dependent dimers observed in crystals of human endostatin.
  Proc Natl Acad Sci U S A, 95, 10443-10448.
PDB code: 1bnl
9249047 M.Betz, P.Huxley, S.J.Davies, Y.Mushtaq, M.Pieper, H.Tschesche, W.Bode, and F.X.Gomis-Rüth (1997).
1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile.
  Eur J Biochem, 247, 356-363.
PDB code: 1kbc
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.  
8662913 C.H.Bu, and T.Pourmotabbed (1996).
Mechanism of Ca2+-dependent activity of human neutrophil gelatinase B.
  J Biol Chem, 271, 14308-14315.  
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.  
8924199 Q.A.Sang, and D.A.Douglas (1996).
Computational sequence analysis of matrix metalloproteinases.
  J Protein Chem, 15, 137-160.  
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.  
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.  
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.  
7629187 C.H.Bu, and T.Pourmotabbed (1995).
Mechanism of activation of human neutrophil gelatinase B. Discriminating between the role of Ca2+ in activation and catalysis.
  J Biol Chem, 270, 18563-18569.  
  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.  
  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.
  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 codes are shown on the right.