Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein

C Paulus; S Hellebrand; U Tessmer; H Wolf; H G Kräusslich; R Wagner

Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein

C Paulus
, S Hellebrand
, U Tessmer
, H Wolf
, H G Kräusslich
, R Wagner

Research output: Contribution to journal › Article › peer-review

Abstract

The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is located between the structural and enzymatic domains of the Gag-Pol polyprotein, flanked by the nucleocapsid (NC) and the protease (PR) domain at its amino and carboxyl termini, respectively. Here, we report that recombinant highly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kinetic analyses and cross-linking experiments revealed a competitive mechanism for PR inhibition by p6*. We further demonstrate that the four carboxyl-terminal residues of p6* are essential but not sufficient for p6*-mediated inhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replication.

Original language	English
Pages (from-to)	21539-43
Number of pages	5
Journal	Journal of Biological Chemistry
Volume	274
Issue number	31
Publication status	Published - 30 Jul 1999

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Amino Acid Sequence
Binding, Competitive
Cross-Linking Reagents
Fusion Proteins, gag-pol
Gene Products, gag
HIV Protease
HIV Protease Inhibitors
Humans
Kinetics
Models, Chemical
Mutagenesis, Site-Directed
Recombinant Proteins
gag Gene Products, Human Immunodeficiency Virus
Journal Article
Research Support, Non-U.S. Gov't

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title = "Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein",

abstract = "The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is located between the structural and enzymatic domains of the Gag-Pol polyprotein, flanked by the nucleocapsid (NC) and the protease (PR) domain at its amino and carboxyl termini, respectively. Here, we report that recombinant highly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kinetic analyses and cross-linking experiments revealed a competitive mechanism for PR inhibition by p6*. We further demonstrate that the four carboxyl-terminal residues of p6* are essential but not sufficient for p6*-mediated inhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replication.",

keywords = "Amino Acid Sequence, Binding, Competitive, Cross-Linking Reagents, Fusion Proteins, gag-pol, Gene Products, gag, HIV Protease, HIV Protease Inhibitors, Humans, Kinetics, Models, Chemical, Mutagenesis, Site-Directed, Recombinant Proteins, gag Gene Products, Human Immunodeficiency Virus, Journal Article, Research Support, Non-U.S. Gov't",

author = "C Paulus and S Hellebrand and U Tessmer and H Wolf and Kr{\"a}usslich, \{H G\} and R Wagner",

year = "1999",

month = jul,

day = "30",

language = "English",

volume = "274",

pages = "21539--43",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

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}

TY - JOUR

T1 - Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein

AU - Paulus, C

AU - Hellebrand, S

AU - Tessmer, U

AU - Wolf, H

AU - Kräusslich, H G

AU - Wagner, R

PY - 1999/7/30

Y1 - 1999/7/30

N2 - The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is located between the structural and enzymatic domains of the Gag-Pol polyprotein, flanked by the nucleocapsid (NC) and the protease (PR) domain at its amino and carboxyl termini, respectively. Here, we report that recombinant highly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kinetic analyses and cross-linking experiments revealed a competitive mechanism for PR inhibition by p6*. We further demonstrate that the four carboxyl-terminal residues of p6* are essential but not sufficient for p6*-mediated inhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replication.

AB - The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is located between the structural and enzymatic domains of the Gag-Pol polyprotein, flanked by the nucleocapsid (NC) and the protease (PR) domain at its amino and carboxyl termini, respectively. Here, we report that recombinant highly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kinetic analyses and cross-linking experiments revealed a competitive mechanism for PR inhibition by p6*. We further demonstrate that the four carboxyl-terminal residues of p6* are essential but not sufficient for p6*-mediated inhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replication.

KW - Amino Acid Sequence

KW - Binding, Competitive

KW - Cross-Linking Reagents

KW - Fusion Proteins, gag-pol

KW - Gene Products, gag

KW - HIV Protease

KW - HIV Protease Inhibitors

KW - Humans

KW - Kinetics

KW - Models, Chemical

KW - Mutagenesis, Site-Directed

KW - Recombinant Proteins

KW - gag Gene Products, Human Immunodeficiency Virus

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Article

C2 - 10419458

SN - 0021-9258

VL - 274

SP - 21539

EP - 21543

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 31

ER -

Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein

Abstract

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Keywords

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