Crystal structure of the catalytic domain of human ADAM33.
Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. We have determined the crystal structure of the Adam33 catalytic domain in complex with the inhibitor marimastat and the inhibitor-free form. The structures reveal the polypeptide fold and active site environment resembling that of other metalloproteases. The substrate-binding site contains unique features that allow the structure-based design of specific inhibitors of this enzyme.
Orth
Peter
P
Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. peter.orth@spcorp.com
Reichert
Paul
P
Wang
Wenyan
W
Prosise
Winifred W
WW
Yarosh-Tomaine
Taisa
T
Hammond
Gerald
G
Ingram
Richard N
RN
Xiao
Li
L
Mirza
Urooj A
UA
Zou
Jun
J
Strickland
Corey
C
Taremi
S Shane
SS
Le
Hung V
HV
Madison
Vincent
V
D051722:ADAM Proteins; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases