1sdu: Difference between revisions

Line 4:

==Overview==

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.

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==

Line 14:

[[Category: Human immunodeficiency virus 1]]

[[Category: Single protein]]

[[Category: Boross, P.I.]]

[[Category: Boross, P I.]]

[[Category: Harrison, R.W.]]

[[Category: Harrison, R W.]]

[[Category: Louis, J.M.]]

[[Category: Louis, J M.]]

[[Category: Mahalingam, B.]]

[[Category: Tozser, J.]]

[[Category: Wang, Y.F.]]

[[Category: Wang, Y F.]]

[[Category: Weber, I.T.]]

[[Category: Weber, I T.]]

[[Category: ACT]]

[[Category: MK1]]

Line 26:

[[Category: drug resistance hiv-1 protease]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Fri~~ Feb 15 16:53:32 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:36 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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==
@@ Line 14: / Line 14: @@
 [[Category: Human immunodeficiency virus 1]]
 [[Category: Single protein]]
-[[Category: Boross, P.I.]]
+[[Category: Boross, P I.]]
-[[Category: Harrison, R.W.]]
+[[Category: Harrison, R W.]]
-[[Category: Louis, J.M.]]
+[[Category: Louis, J M.]]
 [[Category: Mahalingam, B.]]
 [[Category: Tozser, J.]]
-[[Category: Wang, Y.F.]]
+[[Category: Wang, Y F.]]
-[[Category: Weber, I.T.]]
+[[Category: Weber, I T.]]
 [[Category: ACT]]
 [[Category: MK1]]
@@ Line 26: / Line 26: @@
 [[Category: drug resistance hiv-1 protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:53:32 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:36 2008''