1IIQ

CRYSTAL STRUCTURE OF HIV-1 PROTEASE COMPLEXED WITH A HYDROXYETHYLAMINE PEPTIDOMIMETIC INHIBITOR

Summary for 1IIQ

• Entry DOI: 10.2210/pdb1iiq/pdb
• Related: 1FQX
• Related PRD ID: PRD_000384
• Descriptor: PROTEASE RETROPEPSIN, N-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-L-phenylalanyl-L-glutaminyl-L-phenylalaninamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: hiv protease, peptidomimetics, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Cellular location: 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
• Total number of polymer chains: 2
• Total formula weight: 22770.82

Authors

Dohnalek, J.,Hasek, J.,Duskova, J.,Petrokova, H.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Brynda, J.,Sedlacek, J.,Fabry, M. (deposition date: 2001-04-24, release date: 2002-04-12, Last modification date: 2024-03-13)

Primary citation

Dohnalek, J.,Hasek, J.,Duskova, J.,Petrokova, H.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Brynda, J.,Sedlacek, J.,Fabry, M.
Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor.
J.Med.Chem., 45:1432-1438, 2002

PubMed Abstract: A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 A resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors. A comparison with another inhibitor of this series shows that the change of one atom of the P2' side chain (Glu/Gln) leads to an altered ability of creating hydrogen bonds to the active site and within the inhibitor molecule. The diffraction data collected at a synchrotron radiation source enabled a detailed analysis of the complex solvation and of alternative conformations of protein side chains.

PubMed: 11906284
DOI: 10.1021/jm010979e

Experimental method

X-RAY DIFFRACTION (1.83 Å)