Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by GOMIS-RUTH, F. X.
Right arrow Articles by POLITI, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by GOMIS-RUTH, F. X.
Right arrow Articles by POLITI, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Protein Science, Vol 7, Issue 2 283-292, Copyright © 1998 by Cold Spring Harbor Laboratory Press

ARTICLE

Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor {alpha} convertase inhibitors

F. X. GOMIS-RUTH, E. F. MEYER, L. F. KRESS and V. POLITI
Department de Biologia Molecular i Cel.lular, Centre d'Investigacio i Desenvolupament C.S.I.C., Jordi Girona, 18-26, 08034 Barcelona, Spain

Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor {alpha} convertase, TACE, involved in the release of the inflammatory cytokine, TNF{alpha}. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded {beta}-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Infect. Immun.Home page
D. N. Meli, R. S. Coimbra, D. G. Erhart, G. Loquet, C. L. Bellac, M. G. Tauber, U. Neumann, and S. L. Leib
Doxycycline Reduces Mortality and Injury to the Brain and Cochlea in Experimental Pneumococcal Meningitis
Infect. Immun., July 1, 2006; 74(7): 3890 - 3896.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Grantcharova, J. Furkert, H. P. Reusch, H.-W. Krell, G. Papsdorf, M. Beyermann, R. Schulein, W. Rosenthal, and A. Oksche
The Extracellular N Terminus of the Endothelin B (ETB) Receptor Is Cleaved by a Metalloprotease in an Agonist-dependent Process
J. Biol. Chem., November 8, 2002; 277(46): 43933 - 43941.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Pentikainen, A.-M. Hoffren, J. Ivaska, J. Kapyla, T. Nyronen, J. Heino, and M. S. Johnson
"RKKH" Peptides from the Snake Venom Metalloproteinase of Bothrops jararaca Bind Near the Metal Ion-dependent Adhesion Site of the Human Integrin alpha 2 I-domain
J. Biol. Chem., October 29, 1999; 274(44): 31493 - 31505.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Kallberg, M. Gustafsson, B. Persson, J. Thyberg, and J. Johansson
Prediction of Amyloid Fibril-forming Proteins
J. Biol. Chem., April 13, 2001; 276(16): 12945 - 12950.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1998 by The Protein Society.