PDBsum entry 830c

Matrix metalloprotease

PDB id: 830c

Contents

Protein chains

164 a.a. *

Ligands

RS1 ×2

Metals

_ZN ×4

_CA ×2

Waters ×1101

* Residue conservation analysis

PDB id:

830c

Name:

Matrix metalloprotease

Title:

Collagenase-3 (mmp-13) complexed to a sulphone-based hydroxamic acid

Structure:

Mmp-13. Chain: a, b. Fragment: catalytic domain. Synonym: mmp-13. Engineered: yes. Other_details: catalytic domain is complexed with a diphenyl-ether, sulphone inhibitor

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: human cdna construct. Cdna construct of procollagenase-3

Biol. unit:

Monomer (from PDB file)

Resolution:

1.60Å R-factor: 0.208 R-free: 0.266

Authors:

B.Lovejoy,A.Welch,S.Carr,C.Luong,C.Broka,R.T.Hendricks,J.Campbell, K.Walker,R.Martin,H.Van Wart,M.F.Browner

Key ref:

B.Lovejoy et al. (1999). Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat Struct Biol, 6, 217-221. PubMed id: 10074939 DOI: 10.1038/6657

Date:

06-Aug-98 Release date: 06-Aug-99

Protein chains

P45452  (MMP13_HUMAN) -  Collagenase 3 from Homo sapiens

Seq: 471 a.a.

Struc: 164 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.- - ?????

DOI no: 10.1038/6657

Nat Struct Biol 6:217-221 (1999)

PubMed id: 10074939

Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.

B.Lovejoy, A.R.Welch, S.Carr, C.Luong, C.Broka, R.T.Hendricks, J.A.Campbell, K.A.Walker, R.Martin, H.Van Wart, M.F.Browner.

ABSTRACT

The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1.

Selected figure(s)

Figure 2.
Figure 2. The S1' pockets of collagenases-1 and -3. a, Collagense-3 with RS-130830 bound. b, Collagenase-1 with a peptide-based inhibitor (PDB^26, ^27 accession code 2TCL^15). c, Collagenase-1 in a complex with RS-104966. The S1' pockets are represented by a solid surface representation of the enzyme. The S1'-specificity loop is shown by a ribbon, and specificity residue is identified.

Figure 3.
Figure 3. The hydrogen bond interactions of inhibitors bound to collagenases-1 and -3. Collagenase-1 a, with a peptide-based inhibitor (2TCL) and b, with the diphenylether sulfone inhibitor, RS-104966 bound. Collagenase-3 with c, RS-130830 and d, RS-113456 bound.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 217-221) copyright 1999.

Figures were selected by the author.