1A94

STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES

1A94 の概要

• エントリーDOI: 10.2210/pdb1a94/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000349
• 分子名称: PROTEASE, N-[(2R)-2-({N~5~-[amino(iminio)methyl]-L-ornithyl-L-valyl}amino)-4-methylpentyl]-L-phenylalanyl-L-alpha-glutamyl-L-alanyl-L-norleucinamide (3 entities in total)
• 機能のキーワード: human immunodeficiency virus protease, rous sarcoma virus protease, protein-mediated interaction, viral maturation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03367
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 44628.55

構造登録者

Wu, J.,Adomat, J.M.,Ridky, T.W.,Louis, J.M.,Leis, J.,Harrison, R.W.,Weber, I.T. (登録日: 1998-04-16, 公開日: 1999-01-13, 最終更新日: 2024-02-07)

主引用文献

Wu, J.,Adomat, J.M.,Ridky, T.W.,Louis, J.M.,Leis, J.,Harrison, R.W.,Weber, I.T.
Structural basis for specificity of retroviral proteases.
Biochemistry, 37:4518-4526, 1998

PubMed Abstract: The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit high affinity for HIV-1 protease substrates and inhibitors in order to verify the residues deduced to be critical for the specificity differences. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease. Unlike the wild-type enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease polyprotein cleavage sites. The crystal structure of RSV S9 protease with the inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-A resolution. The structure shows flap residues that were not visible in the previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76 are structurally similar to residues 47-59 of HIV-1 protease. However, residues 61-63 form unique loops at the base of the flaps. Mutational analysis indicates that these loop residues are essential for catalytic activity. Side chains of flap residues His 65 and Gln 63' make hydrogen bond interactions with the inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of RSV S9 protease with the CA-p2 analogue are very similar to those observed in the crystal structure of HIV-1 protease with the same inhibitor. This is the first crystal structure of an avian retroviral protease in complex with an inhibitor, and it verifies our knowledge of the molecular basis for specificity differences between RSV and HIV-1 proteases.

PubMed: 9521772
DOI: 10.1021/bi972183g

実験手法

X-RAY DIFFRACTION (2 Å)