1a94

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{{STRUCTURE_1a94| PDB=1a94 | SCENE= }}
{{STRUCTURE_1a94| PDB=1a94 | SCENE= }}
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'''STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES'''
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===STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES===
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==Overview==
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The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit high affinity for HIV-1 protease substrates and inhibitors in order to verify the residues deduced to be critical for the specificity differences. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease. Unlike the wild-type enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease polyprotein cleavage sites. The crystal structure of RSV S9 protease with the inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-A resolution. The structure shows flap residues that were not visible in the previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76 are structurally similar to residues 47-59 of HIV-1 protease. However, residues 61-63 form unique loops at the base of the flaps. Mutational analysis indicates that these loop residues are essential for catalytic activity. Side chains of flap residues His 65 and Gln 63' make hydrogen bond interactions with the inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of RSV S9 protease with the CA-p2 analogue are very similar to those observed in the crystal structure of HIV-1 protease with the same inhibitor. This is the first crystal structure of an avian retroviral protease in complex with an inhibitor, and it verifies our knowledge of the molecular basis for specificity differences between RSV and HIV-1 proteases.
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(as it appears on PubMed at http://www.pubmed.gov), where 9521772 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9521772}}
==About this Structure==
==About this Structure==
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[[Category: Rous sarcoma virus protease]]
[[Category: Rous sarcoma virus protease]]
[[Category: Viral maturation]]
[[Category: Viral maturation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:00:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:25:00 2008''

Revision as of 13:25, 30 June 2008

Image:1a94.png

Template:STRUCTURE 1a94

STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES

Template:ABSTRACT PUBMED 9521772

About this Structure

1A94 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

Reference

Structural basis for specificity of retroviral proteases., Wu J, Adomat JM, Ridky TW, Louis JM, Leis J, Harrison RW, Weber IT, Biochemistry. 1998 Mar 31;37(13):4518-26. PMID:9521772

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