The C-terminal (Haemopexin-Like) Domain Structure of Human Gelatinase A (MMP2): Structural Implications for Its Function

FEBS Lett. 1996 Jan 8;378(2):126-30. doi: 10.1016/0014-5793(95)01435-7.

Abstract

In common with most other matrix metalloproteinases, gelatinase A has a non-catalytic C-terminal domain that displays sequence homology to haemopexin. Crystals of this domain were used by molecular replacement to solve its molecular structure at 2.6 A resolution, which was refined to an R value of 17.9%. This structure has a disc-like shape, with the chain folded into a beta-propeller structure that has pseudo four-fold symmetry. Although the topology and the side-chain arrangement are very similar to the equivalent domain of fibroblast collagenase, significant differences in surface charge and contouring are observable on 1 side of the gelatinase A disc. This difference might be a factor in allowing the gelatinase A C-terminal domain to bind to natural inhibitor TIMP-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • Electrochemistry
  • Gelatinases / chemistry*
  • Gelatinases / metabolism*
  • Hemopexin / chemistry
  • Humans
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / chemistry*
  • Metalloendopeptidases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Peptide Fragments / chemistry*
  • Protease Inhibitors / metabolism
  • Protein Structure, Secondary
  • Proteins / metabolism
  • Sequence Homology
  • Structure-Activity Relationship
  • Swine
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Peptide Fragments
  • Protease Inhibitors
  • Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Hemopexin
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2