PDBsum entry: 1bm6

Metalloprotease

PDB id: 1bm6

Contents

Protein chain

173 a.a. *

Ligands

HAV-3MP-MSB

Metals

_ZN ×2

_CA ×2

* Residue conservation analysis

PDB id:

1bm6

Name:

Metalloprotease

Title:

Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent non-peptidic inhibitor, nmr, 20 structures

Structure:

Stromelysin-1. Chain: a. Synonym: mmp-3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

Y.Li,X.Zhang,R.Melton,V.Ganu,N.C.Gonnella

Key ref:

Y.C.Li et al. (1998). Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor. Biochemistry, 37, 14048-14056. PubMed id: 9760240 DOI: 10.1021/bi981328w

Date:

29-Jul-98 Release date: 29-Jul-99

Protein chain

P08254  (MMP3_HUMAN) -  Stromelysin-1

Seq: 477 a.a.

Struc: 173 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.17 - Stromelysin 1.
• Reaction: Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
• 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: 10.1021/bi981328w

Biochemistry 37:14048-14056 (1998)

PubMed id: 9760240

Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor.

Y.C.Li, X.Zhang, R.Melton, V.Ganu, N.C.Gonnella.

ABSTRACT

The full three-dimensional structure of the catalytic domain of human stromelysin-1 (SCD) complexed to a novel and potent, nonpeptidic inhibitor has been determined by nuclear magnetic resonance spectroscopy (NMR). To accurately mimic assay conditions, the structure was obtained in Tris buffer at pH 6.8 and without the presence of organic solvent. The results showed that the major site of enzyme-inhibitor interaction occurs in the S1' pocket whereas portions of the inhibitor that occupy the shallow S2' and S1 pockets remained primarily solvent exposed. Because this relatively small inhibitor could not deeply penetrate stromelysin's long narrow hydrophobic S1' pocket, the enzyme was found to adopt a dramatic fold in the loop region spanning residues 221-231, allowing occupation of the solvent-accessible S1' channel by the enzyme itself. This remarkable conformational fold at the enzyme binding site resulted in constriction of the S1' loop region about the inhibitor. Examination of the tertiary structure of the stromelysin-inhibitor complex revealed few hydrogen-bonding or hydrophobic interactions between the inhibitor and enzyme that can contribute to overall binding energy; hence the resultant compact structure may in part account for the relatively high potency exhibited by this inhibitor.