1ZJ7

Crystal structure of a complex of mutant HIV-1 protease (A71V, V82T, I84V) with a hydroxyethylamine peptidomimetic inhibitor BOC-PHE-PSI[S-CH(OH)CH2NH]-PHE-GLU-PHE-NH2

Summary for 1ZJ7

• Entry DOI: 10.2210/pdb1zj7/pdb
• Related: 1FQX 1IIQ 1LZQ 1M0B 1Z8C 1ZBG 1ZLF
• Related PRD ID: PRD_000386
• Descriptor: PROTEASE RETROPEPSIN, N-{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-L-phenylalanyl-L-alpha-glutamyl-L-phenylalaninamide (3 entities in total)
• Functional Keywords: hiv, protease, peptidomimetic inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03367
• Total number of polymer chains: 1
• Total formula weight: 11523.58

Authors

Skalova, T.,Dohnalek, J.,Duskova, J.,Petrokova, H.,Hasek, J. (deposition date: 2005-04-28, release date: 2006-05-09, Last modification date: 2023-08-23)

Primary citation

Skalova, T.,Dohnalek, J.,Duskova, J.,Petrokova, H.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Hasek, J.
HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site
J.Med.Chem., 49:5777-5784, 2006

PubMed Abstract: Two new X-ray structures of an HIV-1 protease mutant (A71V, V82T, I84V) in complex with inhibitors SE and SQ, pseudotetrapeptide inhibitors with an acyclic S-hydroxyethylamine isostere, were determined. Comparison of eight structures exploring the binding of four similar inhibitors--SE, SQ (S-hydroxyethylamine isostere), OE (ethyleneamine), and QF34 (hydroxyethylene)--to wild-type and A71V/V82T/I84V HIV-1 protease elucidates the principles of altered interaction with changing conditions. The A71V mutation, which is distant from the active site, causes changes in the structure of the enzyme detectable by the means of X-ray structure analysis, and a route of propagation of the effect toward the active site is proposed.

PubMed: 16970402
DOI: 10.1021/jm0605583

Experimental method

X-RAY DIFFRACTION (1.93 Å)