From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1a30.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1a30.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1a30| PDB=1a30 | SCENE= }} | | {{STRUCTURE_1a30| PDB=1a30 | SCENE= }} |
| | | | |
| - | '''HIV-1 PROTEASE COMPLEXED WITH A TRIPEPTIDE INHIBITOR'''
| + | ===HIV-1 PROTEASE COMPLEXED WITH A TRIPEPTIDE INHIBITOR=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | The HIV-1 transframe region (TFR) is between the structural and functional domains of the Gag-Pol polyprotein, flanked by the nucleocapsid and the protease domains at its N and C termini, respectively. Transframe octapeptide (TFP) Phe-Leu-Arg-Glu-Asp-Leu-Ala-Phe, the N terminus of TFR, and its analogues are competitive inhibitors of the action of the mature HIV-1 protease. The smallest, most potent analogues are tripeptides: Glu-Asp-Leu and Glu-Asp-Phe with Ki values of approximately 50 and approximately 20 microM, respectively. Substitution of the acidic amino acids in the TFP by neutral amino acids and d or retro-d configurations of Glu-Asp-Leu results in an >40-fold increase in Ki. Protease inhibition by Glu-Asp-Leu is dependent on a protonated form of a group with a pKa of 3.8; unlike other inhibitors of HIV-1 protease which are highly hydrophobic, Glu-Asp-Leu is extremely soluble in water, and its binding affinity decreases with increasing NaCl concentration. However, Glu-Asp-Leu is a poor inhibitor (Ki approximately 7.5 mM) of the mammalian aspartic acid protease pepsin. X-ray crystallographic studies at pH 4.2 show that the interactions of Glu at P2 and Leu at P1 of Glu-Asp-Leu with residues of the active site of HIV-1 protease are similar to those of other product-enzyme complexes. It was not feasible to understand the interaction of intact TFP with HIV-1 protease under conditions of crystal growth due to its hydrolysis giving rise to two products. The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-1 replication.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9485357}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9485357 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_9485357}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| | [[Category: Aspartic protease]] | | [[Category: Aspartic protease]] |
| | [[Category: Hiv protease]] | | [[Category: Hiv protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:44:04 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 15:53:19 2008'' |
Revision as of 12:53, 30 June 2008
Template:STRUCTURE 1a30
HIV-1 PROTEASE COMPLEXED WITH A TRIPEPTIDE INHIBITOR
Template:ABSTRACT PUBMED 9485357
About this Structure
1A30 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease., Louis JM, Dyda F, Nashed NT, Kimmel AR, Davies DR, Biochemistry. 1998 Feb 24;37(8):2105-10. PMID:9485357
Page seeded by OCA on Mon Jun 30 15:53:19 2008
