1HEG

The crystal structures at 2.2 angstroms resolution of hydroxyethylene-based inhibitors bound to human immunodeficiency virus type 1 protease show that the inhibitors are present in two distinct orientations

1HEG の概要

• エントリーDOI: 10.2210/pdb1heg/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000320
• 分子名称: HIV-1 PROTEASE, methyl N-{(4S,5S)-5-[(L-alanyl-L-alanyl)amino]-4-hydroxy-6-phenylhexanoyl}-L-valyl-L-valinate (3 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, acid proteinase, 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 : P03366
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11364.38

構造登録者

Murthy, K.,Winborne, E.L.,Minnich, M.D.,Culp, J.S.,Debouck, C. (登録日: 1992-09-21, 公開日: 1994-05-31, 最終更新日: 2024-03-13)

主引用文献

Murthy, K.H.,Winborne, E.L.,Minnich, M.D.,Culp, J.S.,Debouck, C.
The crystal structures at 2.2-A resolution of hydroxyethylene-based inhibitors bound to human immunodeficiency virus type 1 protease show that the inhibitors are present in two distinct orientations.
J.Biol.Chem., 267:22770-22778, 1992

PubMed Abstract: As part of a structure-based drug design program directed against enzyme targets in the human immunodeficiency virus (HIV), we have determined the three-dimensional structures of the HIV type 1 protease complexed with two hydroxyethylene-based inhibitors. The inhibitors (SKF 107457 and SKF 108738) are hexapeptide substrate analogues with the scissile bond being replaced by a hydroxyethylene isostere. The structures were determined using x-ray diffraction data to 2.2 A measured at the Cornell High Energy Synchrotron Source on hexagonal crystals of each of the complexes. The structures have been extensively refined using a reciprocal space least-squares method to conventional crystallographic R factors of 0.186 and 0.159, respectively. The protein structure differs from that in the unliganded state of the enzyme and is most similar to that of the structure of the other reported (Jaskolski, M., Tomasselli, A. G., Sawyer, T. K., Staples, D. G., Heinrikson, R. L., Schneider, J., Kent, S. B. H., and Wlodawer, A. (1990) Biochemistry 29, 5889-5907) hydroxyethylene-based inhibitor complex. Unlike in that structure, however, the inhibitors are observed, in the present crystal structures, in two equally abundant orientations that are a consequence of the homodimeric nature of the enzyme coupled with the asymmetric structures of the inhibitors. Although the differences between the two inhibitors used in the present study are confined to the P1' site, the van der Waals interactions made by the inhibitor atoms with the amino acid residues in the protein differ throughout the structures of the inhibitors.

PubMed: 1429626

実験手法

X-RAY DIFFRACTION (2.2 Å)