Retroviral Proteinases

Oroszlan, Stephen; Luftig, Ronald B.

doi:10.1007/978-3-642-75218-6_6

Cited by 165 publications

(190 citation statements)

References 132 publications

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“…Due to the etiological role of human immunodeficiency virus (HIV) in the development of acquired immunodeficiency syndrome [41, studies have been focussed on the PR of this virus. Recombinant PR or chemically synthesized PR have been purified and used as sources for investigation of enzymatic properties and inhibitor studies (for review see [5][6][7][8][9]). High ionic strength was found to optimize the enzymatic activity by lowering the Michaelis Menten constant (K,0; the turnover number (Kent) was not affected [10,11].…”

Section: Introductionmentioning

confidence: 99%

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

1991

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The effect of different typ~s of salt on the proteolytic activity of H IV. I protease was studied, At a similar ionic strength, the enzyme activity chanlled according to the saltintl out effect of the =ons used (I.lofmeister ~rles), Kinetic studies showed that a stronger saltln$ out effect of tit© ions rather than the higher ionic strength I~r sc increased the affinity to the substrate (K..) but in general did not alter the K.., value, H IV. I pretense; Enzyme kinetics: Salt effect: Hofmeister series

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Section: Introductionmentioning

confidence: 99%

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

1991

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“…[21, Tile polyprotein processing by retroviral PRs, including HIV-I PR, seems to be restricted to the junctions of the protein domains of Gag and Gag-PoI polyproteins [3,4], However, it is difficult to determine a consensus substrata sequence for the retroviral PRs. Although the substrata specificity of retroviral proteinases may partially depend on the proper substrata conformation, the amino acid sequence may have an important role in determining the cleavage sites.…”

Section: Introduction Since the Retroviral Proteinase (Pr) Of The mentioning

confidence: 99%

Studies on the role of the S₄ substrate binding site of HIV proteinases

et al. 1991

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Kinetic una )'sis of the hydrtd~sis of the I~ptide lI.Val,Ser.GIn,Asn.Tyr*Pro.ll¢.VaI.GIn.Nll~ and its analo$,t obtainctl by varyinll the !ength and introduein= substitutions at the P, site was carried out with t~flh HIV.I and ItlV.2 prolein~se~. Deletion or ih¢ t~rmlnal Vtd ~nd Gin had only metier|tie effect on ilia ~uhstrltte hydroly~h, while the d~lation of tli.c P.~. Set ~ts well as P; V,I Ilrcatly reduwd the substrata hydrolysis. Thi~ is pr~dicled to bc due to the loss of Intera,:tions betwoen main ~h~ins of the en,~yme ~ntl thtt substrata. $=bstitution of tile P,~ Ser h:,, amino =raids having high frequency 0f occurrenc~ in//turns resulted in llood substratcs, while larlle ~mino lteids were unfavorable in thi~ position. The two prntai=mses acted similarly, except for substrates havini! TItr, Val and Let= substitutions, which were I~=iler ,o;ommodated in the FIlV.2 substrata bindin$ pocket,

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“…4 -6). Comparison of cleavage site sequences of human immunodeficiency virus type 1 (HIV-1) 1 and type 2 (HIV-2) suggested that the enzyme had a broad specificity and lacked consensus substrate sequence (7). Initially three types of cleavage sites were proposed for HIV-1, HIV-2, and simian immunodeficiency virus (8).…”

mentioning

confidence: 99%

Studies on the Symmetry and Sequence Context Dependence of the HIV-1 Proteinase Specificity

Tőzsér¹,

Bagossi²,

Weber³

et al. 1997

Journal of Biological Chemistry

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Two major types of cleavage sites with different sequence preferences have been proposed for the human immunodeficiency virus type 1 (HIV-1) proteinase. To understand the nature of these sequence preferences better, single and multiple amino acid substitutions were introduced into a type 1 cleavage site peptide, thus changing it to a naturally occurring type 2 cleavage site sequence. Our results indicated that the previous classification of the retroviral cleavage sites may not be generally valid and that the preference for a residue at a particular position in the substrate depends strongly on the neighboring residues, including both those at the same side and at the opposite side of the peptide backbone of the substrate. Based on these results, pseudosymmetric (palindromic) substrates were designed. The retroviral proteinases are symmetrical dimers of two identical subunits; however, the residues of naturally occurring cleavage sites do not show symmetrical arrangements, and no obvious symmetrical substrate preference has been observed for the specificity of HIV proteinase. To examine the role of the asymmetry created by the peptide bonds on the specificity of the respective primed and nonprimed halves of the binding site, amino acid substitutions were introduced into a palindromic sequence. In general, the results suggested that the asymmetry does not result in substantial differences in specificity of the S 3 and S 3 subsites, whereas its effect is more pronounced for the S 2 and S 2 subsites. Although it was possible to design several good palindromic substrates, asymmetrical arrangements may be preferred by the HIV proteinase.

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Retroviral Proteinases

Cited by 165 publications

References 132 publications

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

Studies on the role of the S₄ substrate binding site of HIV proteinases

Studies on the Symmetry and Sequence Context Dependence of the HIV-1 Proteinase Specificity

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Retroviral Proteinases

Cited by 165 publications

References 132 publications

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

The effect of salt on the Michaelis Menten constant of the HIV‐1 protease correlates with the Hofmeister series

Studies on the role of the S4 substrate binding site of HIV proteinases

Studies on the Symmetry and Sequence Context Dependence of the HIV-1 Proteinase Specificity

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Studies on the role of the S₄ substrate binding site of HIV proteinases