1F7A

HOW DOES A SYMMETRIC DIMER RECOGNIZE AN ASYMMETRIC SUBSTRATE? A SUBSTRATE COMPLEX OF HIV-1 PROTEASE.

1F7A の概要

• エントリーDOI: 10.2210/pdb1f7a/pdb
• 分子名称: POL POLYPROTEIN, CA-P2 SUBSTRATE, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: capsid, substrate recognition, hydrolase
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03369
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 23033.12

構造登録者

Schiffer, C.A. (登録日: 2000-06-26, 公開日: 2001-06-27, 最終更新日: 2023-08-09)

主引用文献

Prabu-Jeyabalan, M.,Nalivaika, E.,Schiffer, C.A.
How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease.
J.Mol.Biol., 301:1207-1220, 2000

PubMed Abstract: 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.

PubMed: 10966816
DOI: 10.1006/jmbi.2000.4018

実験手法

X-RAY DIFFRACTION (2 Å)