From Proteopedia
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| | {{STRUCTURE_2fgu| PDB=2fgu | SCENE= }} | | {{STRUCTURE_2fgu| PDB=2fgu | SCENE= }} |
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| - | '''X-ray crystal structure of HIV-1 Protease T80S variant in complex with the inhibitor saquinavir used to explore the role of invariant Thr80 in HIV-1 protease structure, function, and viral infectivity.'''
| + | ===X-ray crystal structure of HIV-1 Protease T80S variant in complex with the inhibitor saquinavir used to explore the role of invariant Thr80 in HIV-1 protease structure, function, and viral infectivity.=== |
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| - | ==Overview==
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| - | Sequence variability associated with human immunodeficiency virus type 1 (HIV-1) is useful for inferring structural and/or functional constraints at specific residues within the viral protease. Positions that are invariant even in the presence of drug selection define critically important residues for protease function. While the importance of conserved active-site residues is easily understood, the role of other invariant residues is not. This work focuses on invariant Thr80 at the apex of the P1 loop of HIV-1, HIV-2, and simian immunodeficiency virus protease. In a previous study, we postulated, on the basis of a molecular dynamics simulation of the unliganded protease, that Thr80 may play a role in the mobility of the flaps of protease. In the present study, both experimental and computational methods were used to study the role of Thr80 in HIV protease. Three protease variants (T80V, T80N, and T80S) were examined for changes in structure, dynamics, enzymatic activity, affinity for protease inhibitors, and viral infectivity. While all three variants were structurally similar to the wild type, only T80S was functionally similar. Both T80V and T80N had decreased the affinity for saquinavir. T80V significantly decreased the ability of the enzyme to cleave a peptide substrate but maintained infectivity, while T80N abolished both activity and viral infectivity. Additionally, T80N decreased the conformational flexibility of the flap region, as observed by simulations of molecular dynamics. Taken together, these data indicate that HIV-1 protease functions best when residue 80 is a small polar residue and that mutations to other amino acids significantly impair enzyme function, possibly by affecting the flexibility of the flap domain.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16809296}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16809296 is the PubMed ID number. |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Protein structure]] | | [[Category: Protein structure]] |
| | [[Category: Sequence conservation]] | | [[Category: Sequence conservation]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:52:41 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:40:47 2008'' |
Revision as of 11:40, 29 July 2008
Template:STRUCTURE 2fgu
X-ray crystal structure of HIV-1 Protease T80S variant in complex with the inhibitor saquinavir used to explore the role of invariant Thr80 in HIV-1 protease structure, function, and viral infectivity.
Template:ABSTRACT PUBMED 16809296
About this Structure
2FGU is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity., Foulkes JE, Prabu-Jeyabalan M, Cooper D, Henderson GJ, Harris J, Swanstrom R, Schiffer CA, J Virol. 2006 Jul;80(14):6906-16. PMID:16809296
Page seeded by OCA on Tue Jul 29 14:40:47 2008
