The NMR structure of the inhibited catalytic domain of human stromelysin-1.
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.
Gooley
P R
PR
Department of Biophysical Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA.
O'Connell
J F
JF
Marcy
A I
AI
Cuca
G C
GC
Salowe
S P
SP
Bush
B L
BL
Hermes
J D
JD
Esser
C K
CK
Hagmann
W K
WK
Springer
J P
JP
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000737:chemistry
D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D015032:Zinc