PDBsum entry: 1hov

Hydrolase/hydrolase inhibitor

PDB id: 1hov

Contents

Protein chain

163 a.a. *

Ligands

I52

Metals

_ZN ×2

_CA ×2

* Residue conservation analysis

PDB id:

1hov

Name:

Hydrolase/hydrolase inhibitor

Title:

Solution structure of a catalytic domain of mmp-2 complexed with sc-74020

Structure:

Matrix metalloproteinase-2. Chain: a. Fragment: catalytic domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

11 models

Authors:

Y.Feng,J.J.Likos,L.Zhu,H.Woodward,G.Munie,J.J.Mcdonald, A.M.Stevens,C.P.Howard,G.A.De Crescenzo,D.Welsch,H.-S.Shieh W.C.Stallings

Key ref:

Y.Feng et al. (2002). Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor. Biochim Biophys Acta, 1598, 10-23. PubMed id: 12147339 DOI: 10.1016/S0167-4838(02)00307-2

Date:

11-Dec-00 Release date: 12-Dec-01

Protein chain

P08253  (MMP2_HUMAN) -  72 kDa type IV collagenase

Seq: 660 a.a.

Struc: 163 a.a.*

* PDB and UniProt seqs differ at 57 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.24.24 - Gelatinase A.
• Reaction: Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.
• Cofactor: Calcium; 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: 10.1016/S0167-4838(02)00307-2

Biochim Biophys Acta 1598:10-23 (2002)

PubMed id: 12147339

Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor.

Y.Feng, J.J.Likos, L.Zhu, H.Woodward, G.Munie, J.J.McDonald, A.M.Stevens, C.P.Howard, G.A.De Crescenzo, D.Welsch, H.S.Shieh, W.C.Stallings.

ABSTRACT

MMP-2 is a member of the matrix metalloproteinase family that has been implicated in tumor cell metastasis and angiogenesis. Here, we describe the solution structure of a catalytic domain of MMP-2 complexed with a hydroxamic acid inhibitor (SC-74020), determined by three-dimensional heteronuclear NMR spectroscopy. The catalytic domain, designated MMP-2C, has a short peptide linker replacing the internal fibronectin-domain insertion and is enzymatically active. Distance geometry-simulated annealing calculations yielded 14 converged structures with atomic root-mean-square deviations (r.m.s.d.) of 1.02 and 1.62 A from the mean coordinate positions for the backbone and for all heavy atoms, respectively, when 11 residues at the N-terminus are excluded. The structure has the same global fold as observed for other MMP catalytic domains and is similar to previously solved crystal structures of MMP-2. Differences observed between the solution and the crystal structures, near the bottom of the S1' specificity loop, appear to be induced by the large inhibitor present in the solution structure. The MMP-2C solution structure is compared with MMP-8 crystal structure bound to the same inhibitor to highlight the differences especially in the S1' specificity loop. The finding provides a structural explanation for the selectivity between MMP-2 and MMP-8 that is achieved by large inhibitors.