1axa
From Proteopedia
(New page: 200px<br /> <applet load="1axa" size="450" color="white" frame="true" align="right" spinBox="true" caption="1axa, resolution 2.0Å" /> '''ACTIVE-SITE MOBILITY...) |
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| - | [[Image:1axa.gif|left|200px]]<br /> | + | [[Image:1axa.gif|left|200px]]<br /><applet load="1axa" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1axa" size=" | + | |
caption="1axa, resolution 2.0Å" /> | caption="1axa, resolution 2.0Å" /> | ||
'''ACTIVE-SITE MOBILITY IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE AS DEMONSTRATED BY CRYSTAL STRUCTURE OF A28S MUTANT'''<br /> | '''ACTIVE-SITE MOBILITY IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE AS DEMONSTRATED BY CRYSTAL STRUCTURE OF A28S MUTANT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The mutation Ala28 to serine in human immunodeficiency virus, type 1, (HIV-1) protease introduces putative hydrogen bonds to each active-site | + | The mutation Ala28 to serine in human immunodeficiency virus, type 1, (HIV-1) protease introduces putative hydrogen bonds to each active-site carboxyl group. These hydrogen bonds are ubiquitous in pepsin-like eukaryotic aspartic proteases. In order to understand the significance of this difference between HIV-1 protease and homologous, eukaryotic aspartic proteases, we solved the three-dimensional structure of A28S mutant HIV-1 protease in complex with a peptidic inhibitor U-89360E. The structure has been determined to 2.0 A resolution with an R factor of 0.194. Comparison of the mutant enzyme structure with that of the wild-type HIV-1 protease bound to the same inhibitor (Hong L, Treharne A, Hartsuck JA, Foundling S, Tang J, 1996, Biochemistry 35:10627-10633) revealed double occupancy for the Ser28 hydroxyl group, which forms a hydrogen bond either to one of the oxygen atoms of the active-site carboxyl or to the carbonyl oxygen of Asp30. We also observed marked changes in orientation of the Asp25 catalytic carboxyl groups, presumably caused by the new hydrogen bonds. These observations suggest that catalytic aspartyl groups of HIV-1 protease have significant conformational flexibility unseen in eukaryotic aspartic proteases. This difference may provide an explanation for some unique catalytic properties of HIV-1 protease. |
==About this Structure== | ==About this Structure== | ||
| - | 1AXA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with U0E 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] Full crystallographic information is available from [http:// | + | 1AXA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=U0E:'>U0E</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ermolieff, J.]] | [[Category: Ermolieff, J.]] | ||
[[Category: Foundling, S.]] | [[Category: Foundling, S.]] | ||
| - | [[Category: Hartsuck, J | + | [[Category: Hartsuck, J A.]] |
[[Category: Hong, L.]] | [[Category: Hong, L.]] | ||
[[Category: Tang, J.]] | [[Category: Tang, J.]] | ||
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[[Category: x-ray]] | [[Category: x-ray]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:49:12 2008'' |
Revision as of 09:49, 21 February 2008
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ACTIVE-SITE MOBILITY IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE AS DEMONSTRATED BY CRYSTAL STRUCTURE OF A28S MUTANT
Overview
The mutation Ala28 to serine in human immunodeficiency virus, type 1, (HIV-1) protease introduces putative hydrogen bonds to each active-site carboxyl group. These hydrogen bonds are ubiquitous in pepsin-like eukaryotic aspartic proteases. In order to understand the significance of this difference between HIV-1 protease and homologous, eukaryotic aspartic proteases, we solved the three-dimensional structure of A28S mutant HIV-1 protease in complex with a peptidic inhibitor U-89360E. The structure has been determined to 2.0 A resolution with an R factor of 0.194. Comparison of the mutant enzyme structure with that of the wild-type HIV-1 protease bound to the same inhibitor (Hong L, Treharne A, Hartsuck JA, Foundling S, Tang J, 1996, Biochemistry 35:10627-10633) revealed double occupancy for the Ser28 hydroxyl group, which forms a hydrogen bond either to one of the oxygen atoms of the active-site carboxyl or to the carbonyl oxygen of Asp30. We also observed marked changes in orientation of the Asp25 catalytic carboxyl groups, presumably caused by the new hydrogen bonds. These observations suggest that catalytic aspartyl groups of HIV-1 protease have significant conformational flexibility unseen in eukaryotic aspartic proteases. This difference may provide an explanation for some unique catalytic properties of HIV-1 protease.
About this Structure
1AXA is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant., Hong L, Hartsuck JA, Foundling S, Ermolieff J, Tang J, Protein Sci. 1998 Feb;7(2):300-5. PMID:9521105
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