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Original title:
Structural basis of HIV-1 and HIV-2 protease inhibition bya monoclonal antibody
Authors: Řezáčová, Pavlína ; Lescar, J. ; Brynda, Jiří ; Fábry, Milan ; Bentley, G. A. ; Sedláček, Juraj
Document type: Papers
Conference/Event: Meetingof the Czech and Slovak structural biologist /2./, Nové Hrady (CZ), 2003-03-13 / 2003-03-15
Year: 2003
Language: eng
Abstract: The murine monoclonal antibody 1696, produced by immunisation with the HIV-1 protease,inhibits the catalytic activity of the enzyme of both the HIV-1 and HIV-2 isolates, with inhibitionconstants in the low nanomolar range. This antibody cross-reacts with peptides that include theN-terminus of the enzyme (residues 1-7), a region which is highly conserved in sequence amongdifferent viral strains and which, furthermore, is crucial for homodimerization to the activeenzymatic form.We report here two crystal structures of a recombinant single-chain Fv fragment of mAb 1696,expressed in E. coli, as a complex with a cross-reactive peptides from the HIV-1 PR and theHIV-2 PR at 2.7 ? resolution and 1.9 ? resolution respectively. On the basis of the interactionsseen in the complex three-dimensional structures, the cross-reactivity between mAb 1696 withthe HIV-1 and HIV-2 protease and their N-terminal peptides can be explained. In addition, acandidate mechanism of HIV PR inhibition by mAb 1696 is proposed which may help thedesign of alternative HIV protease inhibitors, aimed at dissociating the homodimeric viral enzyme.
Keywords: antibody fragment; crystal structure; HIV protease inhibition
Project no.: CEZ:AV0Z5052915 (CEP), GV203/98/K023 (CEP)
Funding provider: GA ČR
Host item entry: Material Structure in Chemistry, Biology, Physics and Technology, ISSN 1211-5894
Institution: Institute of Molecular Genetics AS ČR (web)
Document availability information: Fulltext is available at the institute of the Academy of Sciences.
Original record: http://hdl.handle.net/11104/0087286
Permalink: http://www.nusl.cz/ntk/nusl-28136
The record appears in these collections:
Research > Institutes ASCR > Institute of Molecular Genetics
Conference materials > Papers
Authors: Řezáčová, Pavlína ; Lescar, J. ; Brynda, Jiří ; Fábry, Milan ; Bentley, G. A. ; Sedláček, Juraj
Document type: Papers
Conference/Event: Meetingof the Czech and Slovak structural biologist /2./, Nové Hrady (CZ), 2003-03-13 / 2003-03-15
Year: 2003
Language: eng
Abstract: The murine monoclonal antibody 1696, produced by immunisation with the HIV-1 protease,inhibits the catalytic activity of the enzyme of both the HIV-1 and HIV-2 isolates, with inhibitionconstants in the low nanomolar range. This antibody cross-reacts with peptides that include theN-terminus of the enzyme (residues 1-7), a region which is highly conserved in sequence amongdifferent viral strains and which, furthermore, is crucial for homodimerization to the activeenzymatic form.We report here two crystal structures of a recombinant single-chain Fv fragment of mAb 1696,expressed in E. coli, as a complex with a cross-reactive peptides from the HIV-1 PR and theHIV-2 PR at 2.7 ? resolution and 1.9 ? resolution respectively. On the basis of the interactionsseen in the complex three-dimensional structures, the cross-reactivity between mAb 1696 withthe HIV-1 and HIV-2 protease and their N-terminal peptides can be explained. In addition, acandidate mechanism of HIV PR inhibition by mAb 1696 is proposed which may help thedesign of alternative HIV protease inhibitors, aimed at dissociating the homodimeric viral enzyme.
Keywords: antibody fragment; crystal structure; HIV protease inhibition
Project no.: CEZ:AV0Z5052915 (CEP), GV203/98/K023 (CEP)
Funding provider: GA ČR
Host item entry: Material Structure in Chemistry, Biology, Physics and Technology, ISSN 1211-5894
Institution: Institute of Molecular Genetics AS ČR (web)
Document availability information: Fulltext is available at the institute of the Academy of Sciences.
Original record: http://hdl.handle.net/11104/0087286
Permalink: http://www.nusl.cz/ntk/nusl-28136
The record appears in these collections:
Research > Institutes ASCR > Institute of Molecular Genetics
Conference materials > Papers
Record created 2011-07-01, last modified 2021-11-24