1a8k

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spinqualitylabelsall models 1a8k, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTALLOGRAPHIC ANALYSIS OF HUMAN IMMUNODEFICIENCY VIRUS 1 PROTEASE WITH AN ANALOG OF THE CONSERVED CA-P2 SUBSTRATE: INTERACTIONS WITH FREQUENTLY OCCURRING GLUTAMIC ACID RESIDUE AT P2' POSITION OF SUBSTRATES

Overview

Human immunodeficiency virus type 1 (HIV-1) protease hydrolysis of the Gag, CA-p2 cleavage site is crucial for virion maturation and is optimal at, acidic pH. To understand the processing of the CA-p2 site, we have, determined the structure of HIV-1 protease complexed with an analog of the, CA-p2 site, the reduced peptide inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Ahx-NH2 [r denotes the reduced peptide bond and, Ahx 2-aminohexanoic acid (norleucine), respectively]. The crystal, structure was refined to an R-factor of 0.17 at 0.21-nm resolution. The, crystals have nearly the same lattice as related complexes in, P2(1)2(1)2(1) which have twofold disordered inhibitor, but are in space, group P2(1). and the asymmetric unit contains two dimers of HIV-1 protease, related by 180 degrees rotation. An approximate non-crystallographic, symmetry has replaced the exact crystal symmetry resulting in well-ordered, inhibitor structure. Each protease dimer binds one ordered inhibitor, molecule, but in opposite orientations. The interactions of the inhibitor, with the two dimers are very similar for the central P2 Val to P2' Glu, residues, but show more variation for the distal P3 Arg and P4' Ahx, residues. Importantly, the carboxylate oxygens of Glu at P2' in the, inhibitor are within hydrogen-bonding distance of a carboxylate oxygen of, Asp30 of the protease suggesting that the two side chains share a proton., This interaction suggests that the enzyme-substrate complex is, additionally stabilized at lower pH. The importance of this interaction is, emphasized by the absence of polymorphisms of Asp30 in the protease and, variants of P2' Glu in the critical CA-p2 cleavage site.

About this Structure

1A8K is a Single protein structure of sequence from Human immunodeficiency virus 1 with NH2 as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.

Reference

Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates., Weber IT, Wu J, Adomat J, Harrison RW, Kimmel AR, Wondrak EM, Louis JM, Eur J Biochem. 1997 Oct 15;249(2):523-30. PMID:9370363

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