2aqu

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{{STRUCTURE_2aqu| PDB=2aqu | SCENE= }}
{{STRUCTURE_2aqu| PDB=2aqu | SCENE= }}
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'''Structure of HIV-1 protease bound to atazanavir'''
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===Structure of HIV-1 protease bound to atazanavir===
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==Overview==
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A series of HIV-1 protease mutants has been designed in an effort to analyze the contribution to drug resistance provided by natural polymorphisms as well as therapy-selective (active and non-active site) mutations in the HIV-1 CRF_01 A/E (AE) protease when compared to that of the subtype B (B) protease. Kinetic analysis of these variants using chromogenic substrates showed differences in substrate specificity between pretherapy B and AE proteases. Inhibition analysis with ritonavir, indinavir, nelfinavir, amprenavir, saquinavir, lopinavir, and atazanavir revealed that the natural polymorphisms found in A/E can influence inhibitor resistance. It was also apparent that a high level of resistance in the A/E protease, as with B protease, is due to it aquiring a combination of active site and non-active site mutations. Structural analysis of atazanavir bound to a pretherapy B protease showed that the ability of atazanavir to maintain its binding affinity for variants containing some resistance mutations is due to its unique interactions with flap residues. This structure also explains why the I50L and I84V mutations are important in decreasing the binding affinity of atazanavir.
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The line below this paragraph, {{ABSTRACT_PUBMED_16634628}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16634628 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16634628}}
==About this Structure==
==About this Structure==
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[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:21:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:20:51 2008''

Revision as of 08:20, 28 July 2008

Image:2aqu.png

Template:STRUCTURE 2aqu

Structure of HIV-1 protease bound to atazanavir

Template:ABSTRACT PUBMED 16634628

About this Structure

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

Reference

Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural determinants for maintaining sensitivity and developing resistance to atazanavir., Clemente JC, Coman RM, Thiaville MM, Janka LK, Jeung JA, Nukoolkarn S, Govindasamy L, Agbandje-McKenna M, McKenna R, Leelamanit W, Goodenow MM, Dunn BM, Biochemistry. 2006 May 2;45(17):5468-77. PMID:16634628

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