1bai
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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, ... | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1BAI is a | + | 1BAI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: NUL. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1BAI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: viral maturation]] | [[Category: viral maturation]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:26:45 2007'' |
Revision as of 12:21, 5 November 2007
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STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES
Overview
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.
About this Structure
1BAI is a Single protein structure of sequence from Rous sarcoma virus with NH2 as ligand. Structure known Active Site: NUL. 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
Page seeded by OCA on Mon Nov 5 14:26:45 2007
Categories: Rous sarcoma virus | Single protein | Adomat, J.M. | Harrison, R.W. | Leis, J. | Louis, J.M. | Ridky, T.W. | Weber, I.T. | Wu, J. | NH2 | Complex (protease/inhibitor) | Crystal structures | Human immunodeficiency virus protease | Protein-mediated interaction | Rous sarcoma virus protease | Viral maturation
