Linked Life Data

9370363

Source:http://linkedlifedata.com/resource/pubmed/id/9370363

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-12-12
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
249
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
523-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
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.
pubmed:affiliation
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. weber@asterix.jci.tju.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.