1IVP

THE CRYSTALLOGRAPHIC STRUCTURE OF THE PROTEASE FROM HUMAN IMMUNODEFICIENCY VIRUS TYPE 2 WITH TWO SYNTHETIC PEPTIDIC TRANSITION STATE ANALOG INHIBITORS

1IVP の概要

• エントリーDOI: 10.2210/pdb1ivp/pdb
• 関連するPDBエントリー: 1IVQ
• 関連するBIRD辞書のPRD_ID: PRD_000403
• 分子名称: HIV-2 PROTEASE, 4-[(2R)-3-{[(1S,2S,3R,4S)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methyl-4-({(1S,2R)-2-methyl-1-[(pyridin-2-ylmethyl)carba moyl]butyl}carbamoyl)hexyl]amino}-2-{[(naphthalen-1-yloxy)acetyl]amino}-3-oxopropyl]-1H-imidazol-3-ium (3 entities in total)
• 機能のキーワード: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 2
• 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 : P04584
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22237.65

構造登録者

Mulichak, A.M.,Watenpaugh, K.D. (登録日: 1993-03-18, 公開日: 1993-07-15, 最終更新日: 2024-02-07)

主引用文献

Mulichak, A.M.,Hui, J.O.,Tomasselli, A.G.,Heinrikson, R.L.,Curry, K.A.,Tomich, C.S.,Thaisrivongs, S.,Sawyer, T.K.,Watenpaugh, K.D.
The crystallographic structure of the protease from human immunodeficiency virus type 2 with two synthetic peptidic transition state analog inhibitors.
J.Biol.Chem., 268:13103-13109, 1993

PubMed Abstract: The crystal structure of human immunodeficiency virus (HIV) type 2 protease has been determined in complexes with peptidic inhibitors Noa-His-Cha psi [CH(OH)CH(OH)]Val-Ile-Amp (U75875) and Qnc-Asn-Cha psi [CH(OH)CH2]Val-Npt(U92163) (where Noa is naphthyloxyacetyl, Cha is cyclohexylalanine, Amp is 2-aminomethylpyridine, Qnc is quinoline-2-carbonyl, and Npt is neopentylamine), which have dihydroxyethylene and hydroxyethylene moieties, respectively, in place of the normal scissile bond of the natural ligand. The complexes crystallize in space group P2(1)2(1)2(1), with one dimer-inhibitor complex per asymmetric unit and average cell dimensions of a = 33.28 A, b = 45.35 A, c = 135.84 A. Data were collected to approximately 2.5-A resolution. The model structures were refined with resulting R-factors of around 0.19. As expected, the HIV-2 protease structure is approximately C2-symmetric with a gross structure very similar to that of the HIV-1 enzyme. The inhibitors bind in an extended conformation positioned lengthwise in the binding cleft in a manner similar to that found in the HIV-1 protease-inhibitor complexes previously reported. The substitution of the bulkier Ile82 side chain in the HIV-2 protease may help explain the better ability of HIV-2 protease to bind and hydrolyze ligands with small P1 and P1' side groups. It appears that differences in specificity between the proteases of HIV-1 and HIV-2 are not merely a result of simple side chain substitutions, but may be complicated by differences in main chain flexibility as well.

PubMed: 8514751

実験手法

X-RAY DIFFRACTION (2.5 Å)