1lzq
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(New page: 200px<br /> <applet load="1lzq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lzq, resolution 2.20Å" /> '''Crystal structure o...)
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Revision as of 12:12, 8 November 2007
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Crystal structure of the complex of mutant HIV-1 protease (A71V, V82T, I84V) with an ethylenamine peptidomimetic inhibitor BOC-PHE-PSI[CH2CH2NH]-PHE-GLU-PHE-NH2
Overview
An X-ray structure (resolution 2.2 A) of mutant HIV-1 protease (A71V, V82T, I84V) complexed with a newly developed peptidomimetic inhibitor with, an ethylenamine isostere Boc-Phe-Psi[CH(2)CH(2)NH]-Phe-Glu-Phe-NH(2), denoted as OE, is described and compared with the complex of wild-type, HIV-1 protease with the same inhibitor (resolution 2.5 A). OE shows tight, binding to the wild type (K(i) = 1.5 nM) as well as mutant (K(i) = 4.1 nM), protease. The hydrogen bonds formed, in the case of hydroxyethylamine, inhibitors, by a hydroxyl group are, in the case of OE inhibitors, replaced by a bifurcated hydrogen bond from the isosteric NH group to both, catalytic aspartates Asp 25 and Asp 125. The binding modes of OE inhibitor, to the wild type and mutant protease are similar. However, in the mutant, protease, weaker van der Waals interactions of the mutated residues Val 84, and Val 184 with OE were found. This lack of interaction energy is, compensated by a new aromatic hydrogen bond between the phenyl ring of the, inhibitor in position P1 and the mutated residue Thr 182. Energy analysis, based on molecular mechanics has been performed to distinguish between the, static and dynamic backgrounds of disorder observed at the mutation sites, Thr 82, Val 84, Thr 182, and Val 184.
About this Structure
1LZQ is a Single protein structure of sequence from Human immunodeficiency virus 2 with NH2 and BME as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study., Skalova T, Hasek J, Dohnalek J, Petrokova H, Buchtelova E, Duskova J, Soucek M, Majer P, Uhlikova T, Konvalinka J, J Med Chem. 2003 Apr 24;46(9):1636-44. PMID:12699382
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