A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base

Poorman, Roger A.; Tomasselli, A. G.; Heinrikson, R L; Kézdy, Ferenc J.

doi:10.1016/s0021-9258(18)98722-3

Cited by 167 publications

(44 citation statements)

References 25 publications

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“…HIV protease is similar in active-site structure and mechanism to renin and other aspartyl proteases whose crystal structures have been determined. 176 In contrast to serine and cysteine proteases that center recognition on the P1 position that forms the acyl intermediate, specificity on both sides of the cleavage site precisely orients the scissile amide bond for hydrolysis 177 in HIV proteases. Four rather comprehensive analyses [177][178][179][180] of substrate specificity indicate a strong preference for hydrophobic, unbranched at the ␤-position (Phe, Tyr, Leu, Met) residues at P1.…”

Section: Peptide-enzyme Complexes Proteolytic Enzymesmentioning

confidence: 99%

Peptide interactions with G-protein coupled receptors

Marshall

2001

Biopolymers

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Peptide recognition by G-protein coupled receptors (GPCRs) is reviewed with an emphasis on the indirect approach used to determine the receptor-bound conformation of peptide ligands. This approach was developed in response to the lack of detailed structural information available for these receptors. Recent advances in the structural determination of rhodopsin (the GPCR of the visual system) by crystallography have provided a scaffold for homology modeling of the inactive state of a wide variety of GPCRs that interact with peptide messages. Additionally, the ability to mutate GPCRs and assay compounds of similar chemical structure to test a common binding site on the receptor provides a firm experimental basis for structure-activity studies. Recognition motifs, common in other well-studied systems such as proteolytic enzymes and major histocompatibility class receptors (MHC) are reviewed briefly to provide a basis of comparison. Finally, the development of true peptidomimetics is contrasted with nonpeptide ligands, discovered through combinatorial chemistry. In many systems, the evidence suggests that the peptide ligands bind at the interface between the transmembrane segments and the extracellular loops, while nonpeptide antagonists bind within the transmembrane segments. Plausible models of GPCRs and the mechanism by which they activate G-proteins on binding peptides are beginning to emerge.

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Section: Peptide-enzyme Complexes Proteolytic Enzymesmentioning

confidence: 99%

Peptide interactions with G-protein coupled receptors

Marshall

2001

Biopolymers

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“…There have been many methods for predicting HIV protease cleavage site in proteins, for instance, the h function (Poorman et al, 1991), correlation angle method (Chou, 1993a,b), vector sequence-coupling model (Chou, 1993c), descriminant function method (Chou et al, 1996), feed-forward neural networks with a back-propagation algorithm (Cai and Chou, 1998;Narayanan et al, 2002), binary probabilistic model (Yang, 2001), decision tree methods (Narayanan et al, 2002), bio-basis function neural networks (Thomson et al, 2003) and genetic programming method (Yang et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, 362 HIV octapeptides were collected from (Poorman et al, 1991;Chou, 1996;Chou et al, 1996;Cai and Chou, 1998), of which 114 were positive (with cleavage sites) and 248 negative (without cleavage sites). Here, 300 were randomly selected for training bSVM models and the rest were used for testing.…”

Section: Discussionmentioning

confidence: 99%

Bio-support vector machines for computational proteomics

Yang

Chou

2004

Bioinformatics

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By replacing kernel functions of support vector machines (SVMs) with amino acid similarity measurement matrices, we have modified SVMs, a new type of pattern recognition algorithm for analysing protein sequences, particularly for proteolytic cleavage site prediction. We refer to the modified SVMs as bio-support vector machine. When applied to the prediction of HIV protease cleavage sites, the new method has shown a remarkable advantage in reducing the model complexity and enhancing the model robustness.

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“…Tomasselli et al (1991a,6) have shown that other non-viral proteins are also cleaved by HIV-1 PR: calmodulin, actin, Alzheimer's amyloid precursor protein, troponin C and pro-interleukin 1/3. Detailed analysis of all of these data has enabled Poorman et al (1991) to construct a cumulative cleavage site specificity model for HIV-1 and HIV-2 PRs. Their model proposes that no absolute specificity exists; rather, specificity may result from either a few strong interactions or several moderate interactions between the substrate and HIV-1 PR.…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus type 1 protease microinjected into cultured human skin fibroblasts cleaves vimentin and affects cytoskeletal and nuclear architecture

Höner

Shoeman

Traub

1991

Journal of Cell Science

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In human skin fibroblasts microinjected with purified human immunodeficiency virus type 1 protease (HIV-1 PR), stress fibers were lost and alterations in nuclear morphology and condensation of nuclear chromatin were observed. Thereafter, the vimentin intermediate filament (IF) network collapsed. No effect was seen on the microtubules. While complicated by loss of affected cells from the substratum, a minimum estimate of the proportion of cells demonstrating these effects is 50%. Observation of single cells demonstrated that these effects were largely irreversible and were steps leading to the death of the HIV-1 PR-injected cells. After microinjection of various dilutions of the HIV-1 PR, it was observed that the changes in nuclear morphology and chromatin condensation were detectable under conditions where little or no effect was observed on both stress fibers and the IF network. Proteins of cells labelled with [35S]methionine and microinjected with either HIV-1 PR or BSA were subjected to two-dimensional gel electrophoresis. The major differences in the gel patterns were a diminution in the amount of vimentin and the appearance of novel products comigrating with cleavage products obtained after treatment of vimentin with HIV-1 PR in vitro. Thus, the HIV-1 PR is capable not only of cleaving IF subunit proteins in vivo, but also can catalyze alterations in other cellular structures.

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A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base

Cited by 167 publications

References 25 publications

Peptide interactions with G-protein coupled receptors

Peptide interactions with G-protein coupled receptors

Bio-support vector machines for computational proteomics

Human immunodeficiency virus type 1 protease microinjected into cultured human skin fibroblasts cleaves vimentin and affects cytoskeletal and nuclear architecture

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