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CRYSTAL STRUCTURE OF HIV-1 PROTEASE COMPLEXED WITH A HYDROXYETHYLAMINE PEPTIDOMIMETIC INHIBITORCRYSTAL STRUCTURE OF HIV-1 PROTEASE COMPLEXED WITH A HYDROXYETHYLAMINE PEPTIDOMIMETIC INHIBITOR
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA 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. 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.,Dohnalek J, Hasek J, Duskova J, Petrokova H, Hradilek M, Soucek M, Konvalinka J, Brynda J, Sedlacek J, Fabry M J Med Chem. 2002 Mar 28;45(7):1432-8. PMID:11906284[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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