Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer.
AuthorsMatayoshi ED, Wang GT, Krafft GA, Erickson J
JournalScience
PubMed ID2106161
'The 11-kD protease (PR) encoded by the human immunodeficiency virus 1 (HIV-1) is essential for the correct processing of viral polyproteins and the maturation of infectious virus, and is therefore a target for the design of selective acquired immunodeficiency syndrome (AIDS) therapeutics. To facilitate the identification of novel inhibitors of ... More
Reversible S-nitrosation and inhibition of HIV-1 protease.
AuthorsSehajpal PK, Basu A, Ogiste JS, Lander HM
JournalBiochemistry
PubMed ID10529217
'Nitric oxide (*NO) is a short-lived free radical with many functions including vasoregulation, synaptic plasticity, and immune modulation and has recently been associated with AIDS pathology. Various pathophysiological conditions, such as viral infection, trigger inducible nitric oxide synthase (iNOS) to synthesize NO in the cell. NO-derived species can react with ... More
A transient precursor of the HIV-1 protease. Isolation, characterization, and kinetics of maturation.
AuthorsWondrak EM, Nashed NT, Haber MT, Jerina DM, Louis JM
JournalJ Biol Chem
PubMed ID8626801
'Recently, the mechanism of autoprocessing of the protease (PR) of the human immunodeficiency virus type 1 from the model polyprotein, MBP-DeltaTF-PR-DeltaPol, which contains the protease linked to short native flanking sequences (DeltaTF and DeltaPol) fused to the maltose binding protein (MBP) of Escherichia coli, was reported (Louis, J. M., Nashed, ... More
Genetic selection for dissociative inhibitors of designated protein-protein interactions.
AuthorsPark SH, Raines RT
JournalNat Biotechnol
PubMed ID10932153
'Many biological processes rely on protein-protein interactions. These processes include signal transduction, cell cycle regulation, gene regulation, and viral assembly and replication. Moreover, many proteins and enzymes manifest their function as oligomers. We describe here an efficient means to sift through large combinatorial libraries and identify molecules that block the ... More
Additivity in the analysis and design of HIV protease inhibitors.
AuthorsJorissen RN, Reddy GS, Ali A, Altman MD, Chellappan S, Anjum SG, Tidor B, Schiffer CA, Rana TM, Gilson MK,
JournalJ Med Chem
PubMed ID19193159
'We explore the applicability of an additive treatment of substituent effects to the analysis and design of HIV protease inhibitors. Affinity data for a set of inhibitors with a common chemical framework were analyzed to provide estimates of the free energy contribution of each chemical substituent. These estimates were then ... More
Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease.
AuthorsErickson J, Neidhart DJ, VanDrie J, Kempf DJ, Wang XC, Norbeck DW, Plattner JJ, Rittenhouse JW, Turon M, Wideburg N
JournalScience
PubMed ID2200122
A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 ... More
Conformational selectivity of HIV-1 protease cleavage of X-Pro peptide bonds and its implications.
AuthorsVance JE, LeBlanc DA, Wingfield P, London RE
JournalJ Biol Chem
PubMed ID9188447
Kinetic measurements on a fluorescent peptide analog of the p17/p24 cleavage site of the Gag polyprotein demonstrate the conformational selectivity of human immunodeficiency virus, type 1 protease for the trans conformation of the Tyr-Pro bond. A mean cis/trans ratio of 0. 3, and a cis --> trans isomerization rate constant ... More
Activity and dimerization of human immunodeficiency virus protease as a function of solvent composition and enzyme concentration.
AuthorsJordan SP, Zugay J, Darke PL, Kuo LC
JournalJ Biol Chem
PubMed ID1400318
The activity of human immunodeficiency virus 1 (HIV-1) protease has been examined as a function of solvent composition, incubation time, and enzyme concentration at 37 degrees C in the pH 4.5-5.5 range. Glycerol and dimethyl sulfoxide inhibit the enzyme, while polyethylene glycol and bovine serum albumin activate the enzyme. When ... More
Application of fluorescence resonance energy transfer in the clinical laboratory: routine and research.
AuthorsSzöllosi J, Damjanovich S, Mátyus L
JournalCytometry
PubMed ID9725457
Fluorescence resonance energy transfer (FRET) phenomenon has been applied to a variety of scientific challenges in the past. The potential utility of this biophysical tool will be revisited in the 21st century. The rapid digital signal processing in conjunction with personal computers and the wide use of multicolor laser technology ... More