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 HONG, L.
Right arrow Articles by TANG, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by HONG, L.
Right arrow Articles by TANG, J.
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 2 300-305, Copyright © 1998 by Cold Spring Harbor Laboratory Press

ARTICLE

Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant

L. HONG, J. A. HARTSUCK, S. FOUNDLING, J. ERMOLIEFF and J. TANG
Protein Studies, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104

The mutation Ala(28) to serine in human immunodeficiency virus, type 1, (HIV-1) protease introduces putative hydrogen bonds to each active-site carboxyl group. These hydrogen bonds are ubiquitous in pepsin-like eukaryotic aspartic proteases. In order to understand the significance of this difference between HIV-1 protease and homologous, eukaryotic aspartic proteases, we solved the three-dimensional structure of A28S mutant HIV-1 protease in complex with a peptidic inhibitor U-89360E. The structure has been determined to 2.0 A resolution with an R factor of 0.194. Comparison of the mutant enzyme structure with that of the wild-type HIV-1 protease bound to the same inhibitor (Hong L, Treharne A, Hartsuck JA, Foundling S, Tang J, 1996, Biochemistry 35:10627-10633) revealed double occupancy for the Ser(28) hydroxyl group, which forms a hydrogen bond either to one of the oxygen atoms of the active-site carboxyl or to the carbonyl oxygen of Asp(30). We also observed marked changes in orientation of the Asp(25) catalytic carboxyl groups, presumably caused by the new hydrogen bonds. These observations suggest that catalytic aspartyl groups of HIV-1 protease have significant conformational flexibility unseen in eukaryotic aspartic proteases. This difference may provide an explanation for some unique catalytic properties of HIV-1 protease.
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
 Antimicrob. Agents Chemother.Home page
M. Amano, Y. Koh, D. Das, J. Li, S. Leschenko, Y.-F. Wang, P. I. Boross, I. T. Weber, A. K. Ghosh, and H. Mitsuya
A Novel Bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI), GRL-98065, Is Potent against Multiple-PI-Resistant Human Immunodeficiency Virus In Vitro
Antimicrob. Agents Chemother., June 1, 2007; 51(6): 2143 - 2155.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
P. J. Yates, R. Hazen, M. St. Clair, L. Boone, M. Tisdale, and R. C. Elston
In Vitro Development of Resistance to Human Immunodeficiency Virus Protease Inhibitor GW640385
Antimicrob. Agents Chemother., March 1, 2006; 50(3): 1092 - 1095.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
K. Yoshimura, R. Kato, M. F. Kavlick, A. Nguyen, V. Maroun, K. Maeda, K. A. Hussain, A. K. Ghosh, S. V. Gulnik, J. W. Erickson, et al.
A Potent Human Immunodeficiency Virus Type 1 Protease Inhibitor, UIC-94003 (TMC-126), and Selection of a Novel (A28S) Mutation in the Protease Active Site
J. Virol., February 1, 2002; 76(3): 1349 - 1358.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
N. M. King, L. Melnick, M. Prabu-Jeyabalan, E. A. Nalivaika, S.-S. Yang, Y. Gao, X. Nie, C. Zepp, D. L. Heefner, and C. A. Schiffer
Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease
Protein Sci., February 1, 2002; 11(2): 418 - 429.
[Abstract] [Full Text] [PDF]


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