1sdt: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
The crystal structures of the wild-type HIV-1 protease (PR) and the two | The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10-15%, in their k(cat)/K(m) values relative to PR. The crystal structures were refined to resolutions of 1.25-1.4 A to reveal critical features associated with inhibitor resistance. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. These structural differences concur with the kinetic data. | ||
==About this Structure== | ==About this Structure== | ||
| Line 14: | Line 14: | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Boross, P | [[Category: Boross, P I.]] | ||
[[Category: Harrison, R | [[Category: Harrison, R W.]] | ||
[[Category: Louis, J | [[Category: Louis, J M.]] | ||
[[Category: Mahalingam, B.]] | [[Category: Mahalingam, B.]] | ||
[[Category: Tozser, J.]] | [[Category: Tozser, J.]] | ||
[[Category: Wang, Y | [[Category: Wang, Y F.]] | ||
[[Category: Weber, I | [[Category: Weber, I T.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
[[Category: MK1]] | [[Category: MK1]] | ||
[[Category: drug resistance; hiv-1]] | [[Category: drug resistance; hiv-1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:32 2008'' | ||
Revision as of 16:00, 21 February 2008
|
Crystal structures of HIV protease V82A and L90M mutants reveal changes in indinavir binding site.
OverviewOverview
The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10-15%, in their k(cat)/K(m) values relative to PR. The crystal structures were refined to resolutions of 1.25-1.4 A to reveal critical features associated with inhibitor resistance. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. These structural differences concur with the kinetic data.
About this StructureAbout this Structure
1SDT is a Single protein structure of sequence from Human immunodeficiency virus 1 with and as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site., Mahalingam B, Wang YF, Boross PI, Tozser J, Louis JM, Harrison RW, Weber IT, Eur J Biochem. 2004 Apr;271(8):1516-24. PMID:15066177
Page seeded by OCA on Thu Feb 21 15:00:32 2008