1f7a
From Proteopedia
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'''HOW DOES A SYMMETRIC DIMER RECOGNIZE AN ASYMMETRIC SUBSTRATE? A SUBSTRATE COMPLEX OF HIV-1 PROTEASE.''' | '''HOW DOES A SYMMETRIC DIMER RECOGNIZE AN ASYMMETRIC SUBSTRATE? A SUBSTRATE COMPLEX OF HIV-1 PROTEASE.''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Schiffer, C A.]] | [[Category: Schiffer, C A.]] | ||
- | [[Category: | + | [[Category: Capsid]] |
- | [[Category: | + | [[Category: Substrate recognition]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:59:22 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 12:59, 2 May 2008
HOW DOES A SYMMETRIC DIMER RECOGNIZE AN ASYMMETRIC SUBSTRATE? A SUBSTRATE COMPLEX OF HIV-1 PROTEASE.
Overview
The crystal structure of an actual HIV-1 protease-substrate complex is presented at 2.0 A resolution (R-value of 19.7 % (R(free) 23.3 %)) between an inactive variant (D25N) of HIV-1 protease and a long substrate peptide, Lys-Ala-Arg-Val-Leu-Ala-Glu-Ala-Met-Ser, which covers a full binding epitope of capsid(CA)-p2, cleavage site. The substrate peptide is asymmetric in both size and charge distribution. To accommodate this asymmetry the two protease monomers adopt different conformations burying a total of 1038 A(2) of surface area at the protease-substrate interface. The specificity for the CA-p2 substrate peptide is mainly hydrophobic, as most of the hydrogen bonds are made with the backbone of the peptide substrate. Two water molecules bridge the two monomers through the loops Gly49-Gly52 (Gly49'-Gly52') and Pro79'-Val82' (Pro79-Val82). When other complexes are compared, the mobility of these loops is correlated with the content of the P1 and P1' sites. Interdependence of the conformational changes allows the protease to exhibit its wide range of substrate specificity.
About this Structure
1F7A is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease., Prabu-Jeyabalan M, Nalivaika E, Schiffer CA, J Mol Biol. 2000 Sep 1;301(5):1207-20. PMID:10966816 Page seeded by OCA on Fri May 2 15:59:22 2008