The NMR structure of the inhibited catalytic domain of human stromelysin-1

P R Gooley; J F O'Connell; A I Marcy; G C Cuca; S P Salowe; B L Bush; J D Hermes; C K Esser; W K Hagmann; J P Springer

doi:10.1038/nsb0294-111

The NMR structure of the inhibited catalytic domain of human stromelysin-1

Nat Struct Biol. 1994 Feb;1(2):111-8. doi: 10.1038/nsb0294-111.

Authors

P R Gooley¹, J F O'Connell, A I Marcy, G C Cuca, S P Salowe, B L Bush, J D Hermes, C K Esser, W K Hagmann, J P Springer, et al.

Affiliation

¹ Department of Biophysical Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA.

PMID: 7656014
DOI: 10.1038/nsb0294-111

Abstract

The three-dimensional structure of the catalytic domain of stromelysin-1 complexed with an N-carboxyl alkyl inhibitor has been determined by NMR methods. The global fold consists of three helices, a five stranded beta-sheet and a methionine located in a turn near the catalytic histidines, classifying stromelysin-1 as a metzincin. Stromelysin-1 is unique in having two independent zinc binding sites: a catalytic site and a structural site. The inhibitor binds in an extended conformation. The S1' subsite is a deep hydrophobic pocket, whereas S2' appears shallow and S3' open.

Publication types

Comparative Study

MeSH terms

Amino Acid Sequence
Binding Sites
Catalysis
Humans
In Vitro Techniques
Magnetic Resonance Spectroscopy
Matrix Metalloproteinase 3
Metalloendopeptidases / antagonists & inhibitors*
Metalloendopeptidases / chemistry*
Metalloendopeptidases / genetics
Models, Molecular
Molecular Sequence Data
Molecular Structure
Protein Conformation
Protein Folding
Sequence Homology, Amino Acid
Zinc / chemistry

Substances

Metalloendopeptidases
Matrix Metalloproteinase 3
Zinc