PDBsum entry: 1g05

Hydrolase

PDB-id: 1g05

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

166 a.a. *

Ligands

BBH

Metal ions

_CA ×6

_ZN ×4

Waters ×44

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1g05

Name:

Hydrolase

Title:

Heterocycle-based mmp inhibitor with p2'substituents

Structure:

Stromelysin-1 precursor. Chain: a, b. Fragment: catalytic domain. Synonym: mmp-3. Engineered: yes

Source:

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

UniProt:

Chains A, B: P08254 (MMP3_HUMAN)

Seq:

Struc:

Seq:

477 a.a.

Struc:

166 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Enzyme class:

E.C.3.4.24.17   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

Preferential cleavage where P1', P2' and P3' are hydrophobic residues.

Cofactor:

Calcium; Zinc

Resolution:

2.45Å

R-factor:

0.246

R-free:

0.293

Authors:

S.Pikul,K.M.Dunham,N.G.Almstead,B.De,M.G.Natchus,Y.O.Taiwo, L.E.Williams,B.A.Hynd,L.C.Hsieh,M.J.Janusz

Key ref:

S.Pikul et al. (2001). Heterocycle-based MMP inhibitors with P2' substituents.. Bioorg Med Chem Lett, 11, 1009-1013. [PubMed id: 11327577] [DOI: 10.1016/S0960-894X(01)00137-8]

Date:

05-Oct-00

Release date:

05-Oct-01

Related entries:

1cqr
1cqr contains the same protein complexed with a different
inhibitor.
1d5j
1d5j contains the same protein complexed with a different
inhibitor.
1d7x
1d7x contains the same protein complexed with a different
inhibitor.
1d8f
... plus others (see Header records)

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1016/S0960-894X(01)00137-8

Bioorg Med Chem Lett 11:1009-1013 (2001)

PubMed id: 11327577

Heterocycle-based MMP inhibitors with P2' substituents.

S.Pikul, K.M.Dunham, N.G.Almstead, B.De, M.G.Natchus, Y.O.Taiwo, L.E.Williams, B.A.Hynd, L.C.Hsieh, M.J.Janusz, F.Gu, G.E.Mieling.

ABSTRACT

Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.