This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1sgu

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1sgu.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1sgu.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1sgu| PDB=1sgu | SCENE= }}
{{STRUCTURE_1sgu| PDB=1sgu | SCENE= }}
-
'''Comparing the Accumulation of Active Site and Non-active Site Mutations in the HIV-1 Protease'''
+
===Comparing the Accumulation of Active Site and Non-active Site Mutations in the HIV-1 Protease===
-
==Overview==
+
<!--
-
Protease inhibitor resistance still poses one of the greatest challenges in treating HIV. To better design inhibitors able to target resistant proteases, a deeper understanding is needed of the effects of accumulating mutations and the contributions of active- and nonactive-site mutations to the resistance. We have engineered a series of variants containing the nonactive-site mutations M46I and I54V and the active-site mutation I84V. These mutations were added to a protease clone (V6) isolated from a pediatric patient on ritonavir therapy. This variant possessed the ritonavir-resistance-associated mutations in the active-site (V32I and V82A) and nonactive-site mutations (K20R, L33F, M36I, L63P, A71V, and L90M). The I84V mutation had the greatest effect on decreasing catalytic efficiency, 10-fold when compared to the pretherapy clone LAI. The decrease in catalytic efficiency was partially recovered by the addition of mutations M46I and I54V. The M46I and I54V were just as effective at decreasing inhibitor binding as the I84V mutation when compared to V6 and LAI. The V6(54/84) variant showed over 1000-fold decrease in inhibitor-binding strength to ritonavir, indinavir, and nelfinavir when compared to LAI and V6. Crystal-structure analysis of the V6(54/84) variant bound to ritonavir and indinavir shows structural changes in the 80's loops and active site, which lead to an enlarged binding cavity when compared to pretherapy structures in the Protein Data Bank. Structural changes are also seen in the 10's and 30's loops, which suggest possible changes in the dynamics of flap opening and closing.
+
The line below this paragraph, {{ABSTRACT_PUBMED_15379553}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 15379553 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_15379553}}
==About this Structure==
==About this Structure==
Line 36: Line 40:
[[Category: Indinavir]]
[[Category: Indinavir]]
[[Category: Non-active site mutation]]
[[Category: Non-active site mutation]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:41:14 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:09:59 2008''

Revision as of 03:10, 29 July 2008

Image:1sgu.png

Template:STRUCTURE 1sgu

Comparing the Accumulation of Active Site and Non-active Site Mutations in the HIV-1 Protease

Template:ABSTRACT PUBMED 15379553

About this Structure

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

Reference

Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease., Clemente JC, Moose RE, Hemrajani R, Whitford LR, Govindasamy L, Reutzel R, McKenna R, Agbandje-McKenna M, Goodenow MM, Dunn BM, Biochemistry. 2004 Sep 28;43(38):12141-51. PMID:15379553

Page seeded by OCA on Tue Jul 29 06:09:59 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sgu"
Personal tools