PDBsum entry: 1cgf

Hydrolase (metalloprotease)

PDB id: 1cgf

Contents

Protein chains

162 a.a. *

Metals

_CA ×6

_ZN ×4

Waters ×543

* Residue conservation analysis

PDB id:

1cgf

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

Resolution:

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

Date:

03-Feb-94 Release date: 31-Mar-95

Protein chains

P03956  (MMP1_HUMAN) -  Interstitial collagenase

Seq: 469 a.a.

Struc: 162 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.24.7 - Interstitial collagenase.
• 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: Zinc

 Gene Ontology (GO) functional annotation 

• 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.

ABSTRACT

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.