2fnt

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{{STRUCTURE_2fnt| PDB=2fnt | SCENE= }}
{{STRUCTURE_2fnt| PDB=2fnt | SCENE= }}
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'''Crystal structure of a drug-resistant (V82A) inactive (D25N) HIV-1 protease complexed with AP2V variant of HIV-1 NC-p1 substrate.'''
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===Crystal structure of a drug-resistant (V82A) inactive (D25N) HIV-1 protease complexed with AP2V variant of HIV-1 NC-p1 substrate.===
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==Overview==
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Human immunodeficiency virus type 1 (HIV-1) protease processes and cleaves the Gag and Gag-Pol polyproteins, allowing viral maturation, and therefore is an important target for antiviral therapy. Ligand binding occurs when the flaps open, allowing access to the active site. This flexibility in flap geometry makes trapping and crystallizing structural intermediates in substrate binding challenging. In this study, we report two crystal structures of two HIV-1 protease variants bound with their corresponding nucleocapsid-p1 variant. One of the flaps in each of these structures exhibits an unusual "intermediate" conformation. Analysis of the flap-intermediate and flap-closed crystal structures reveals that the intermonomer flap movements may be asynchronous and that the flap which wraps over the P3 to P1 (P3-P1) residues of the substrate might close first. This is consistent with our hypothesis that the P3-P1 region is crucial for substrate recognition. The intermediate conformation is conserved in both the wild-type and drug-resistant variants. The structural differences between the variants are evident only when the flaps are closed. Thus, a plausible structural model for the adaptability of HIV-1 protease to recognize substrates in the presence of drug-resistant mutations has been proposed.
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(as it appears on PubMed at http://www.pubmed.gov), where 16537628 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16537628}}
==About this Structure==
==About this Structure==
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[[Category: Structural intermediate]]
[[Category: Structural intermediate]]
[[Category: Substrate recognition]]
[[Category: Substrate recognition]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:06:43 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:52:02 2008''

Revision as of 11:52, 29 July 2008

Image:2fnt.png

Template:STRUCTURE 2fnt

Crystal structure of a drug-resistant (V82A) inactive (D25N) HIV-1 protease complexed with AP2V variant of HIV-1 NC-p1 substrate.

Template:ABSTRACT PUBMED 16537628

About this Structure

2FNT is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

Reference

Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate., Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA, J Virol. 2006 Apr;80(7):3607-16. PMID:16537628

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