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| {{STRUCTURE_1b92| PDB=1b92 | SCENE= }} | | {{STRUCTURE_1b92| PDB=1b92 | SCENE= }} |
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| '''MOBILITY OF AN HIV-1 INTEGRASE ACTIVE SITE LOOP IS CORRELATED WITH CATALYTIC ACTIVITY'''
| | ===MOBILITY OF AN HIV-1 INTEGRASE ACTIVE SITE LOOP IS CORRELATED WITH CATALYTIC ACTIVITY=== |
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| ==Overview==
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| Replication of HIV-1 requires the covalent integration of the viral cDNA into the host chromosomal DNA directed by the virus-encoded integrase protein. Here we explore the importance of a protein surface loop near the integrase active site using protein engineering and X-ray crystallography. We have redetermined the structure of the integrase catalytic domain (residues 50-212) using an independent phase set at 1.7 A resolution. The structure extends helix alpha4 on its N-terminal side (residues 149-154), thus defining the position of the three conserved active site residues. Evident in this and in previous structures is a conformationally flexible loop composed of residues 141-148. To probe the role of flexibility in this loop, we replaced Gly 140 and Gly 149, residues that appear to act as conformational hinges, with Ala residues. X-ray structures of the catalytic domain mutants G149A and G140A/G149A show further rigidity of alpha4 and the adjoining loop. Activity assays in vitro revealed that these mutants are impaired in catalysis. The DNA binding affinity, however, is minimally affected by these mutants as assayed by UV cross-linking. We propose that the conformational flexibility of this active site loop is important for a postbinding catalytic step.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10413462}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10413462 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10413462}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Le, V.]] | | [[Category: Le, V.]] |
| [[Category: Dna integration,transferase]] | | [[Category: Dna integration,transferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:13:37 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:36:11 2008'' |