1w5y: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1w5y.gif|left|200px]]<br /> | [[Image:1w5y.gif|left|200px]]<br /><applet load="1w5y" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1w5y" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1w5y, resolution 1.90Å" /> | caption="1w5y, resolution 1.90Å" /> | ||
'''HIV-1 PROTEASE IN COMPLEX WITH FLUORO SUBSTITUTED DIOL-BASED C2-SYMMETRIC INHIBITOR'''<br /> | '''HIV-1 PROTEASE IN COMPLEX WITH FLUORO SUBSTITUTED DIOL-BASED C2-SYMMETRIC INHIBITOR'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
1W5Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus] with BE6 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] | 1W5Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus] with BE6 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Known structural/functional Site: <scene name='pdbsite=AC1:Be6 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W5Y OCA]. | ||
==Reference== | ==Reference== | ||
| Line 32: | Line 31: | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:31:48 2007'' | ||
Revision as of 19:22, 18 December 2007
|
HIV-1 PROTEASE IN COMPLEX WITH FLUORO SUBSTITUTED DIOL-BASED C2-SYMMETRIC INHIBITOR
OverviewOverview
HIV-1 protease is a pivotal enzyme in the later stages of the viral life, cycle which is responsible for the processing and maturation of the virus, particle into an infectious virion. As such, HIV-1 protease has become an, important target for the treatment of AIDS, and efficient drugs have been, developed. However, negative side effects and fast emerging resistance to, the current drugs have necessitated the development of novel chemical, entities in order to exploit different pharmacokinetic properties as well, as new interaction patterns. We have used X-ray crystallography to, decipher the structure-activity relationship of fluoro-substitution as a, strategy to improve the antiviral activity and the protease inhibition of, C2-symmetric diol-based inhibitors. In total we present six, protease-inhibitor complexes at 1.8-2.3 A resolution, which have been, structurally characterized with respect to their antiviral and inhibitory, activities, in order to evaluate the effects of different, fluoro-substitutions. These C2-symmetric inhibitors comprise mono- and, difluoro-substituted benzyloxy side groups in P1/P1' and indanoleamine, side groups in P2/P2'. The ortho- and meta-fluorinated P1/P1'-benzyloxy, side groups proved to have the most cytopathogenic effects compared with, the nonsubstituted analog and related C2-symmetric diol-based inhibitors., The different fluoro-substitutions are well accommodated in the protease, S1/S1' subsites, as observed by an increase in favorable Van der Waals, contacts and surface area buried by the inhibitors. These data will be, used in the development of potent inhibitors with different, pharmacokinetic profiles towards resistant protease mutants.
About this StructureAbout this Structure
1W5Y is a Single protein structure of sequence from Human immunodeficiency virus with BE6 as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Symmetric fluoro-substituted diol-based HIV protease inhibitors. Ortho-fluorinated and meta-fluorinated P1/P1'-benzyloxy side groups significantly improve the antiviral activity and preserve binding efficacy., Lindberg J, Pyring D, Lowgren S, Rosenquist A, Zuccarello G, Kvarnstrom I, Zhang H, Vrang L, Classon B, Hallberg A, Samuelsson B, Unge T, Eur J Biochem. 2004 Nov;271(22):4594-602. PMID:15560801
Page seeded by OCA on Tue Dec 18 18:31:48 2007