High-resolution structure of unbound human immunodeficiency virus 1 subtype C protease: implications of flap dynamics and drug resistance.
Acta Crystallogr D Biol Crystallogr
; D64(Pt 7): 754-63, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18566511
ABSTRACT
The X-ray crystal structure of the unbound state of human immunodeficiency virus 1 (HIV-1) subtype C protease (C PR) has been determined to 1.20 angstroms resolution in the tetragonal space group P4(1)2(1)2, with one monomer per asymmetric unit and unit-cell parameters a = 46.7, c = 100.8 angstroms, allowing full anisotropic least-squares refinement. The refined model has a conventional R factor of 14.1% for all reflections and estimated standard deviations in bond lengths and angles for all main-chain non-H atoms of 0.014 angstroms and 0.030 degrees , respectively. The structure is compared with three unbound subtype B proteases (B PRs) to identify structural changes arising from the naturally occurring polymorphisms and delineate their implications in antiretroviral drug resistance/susceptibility. The unbound C PR exhibits a larger distance between the tips of the flaps, a downward displacement of the 36-41 loop and an increased thermal stability of the 10s loop when compared with the B PR structures. The C PR structure presents the highest resolution of the unbound state of a non-subtype-B PR and adds to the understanding of flap dynamics and drug resistance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteasa del VIH
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Acta Crystallogr D Biol Crystallogr
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
/
UNITED STATES OF AMERICA
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US
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USA