1nh0
From Proteopedia
(New page: 200px<br /> <applet load="1nh0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nh0, resolution 1.03Å" /> '''1.03 A structure of...) |
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caption="1nh0, resolution 1.03Å" /> | caption="1nh0, resolution 1.03Å" /> | ||
'''1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site'''<br /> | '''1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The X-ray structure of a complex of HIV-1 protease (PR) with a | + | The X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses. |
==About this Structure== | ==About this Structure== | ||
| - | 1NH0 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 SO4, NH2 and BME as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1NH0 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=SO4:'>SO4</scene>, <scene name='pdbligand=NH2:'>NH2</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1NH0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: inhibitor design]] | [[Category: inhibitor design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:05:59 2008'' |
Revision as of 12:06, 21 February 2008
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1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site
Overview
The X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses.
About this Structure
1NH0 is a Single protein structure of sequence from Human immunodeficiency virus 1 with , and as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation, and subsite-pocket interactions analyzed at atomic resolution., Brynda J, Rezacova P, Fabry M, Horejsi M, Stouracova R, Sedlacek J, Soucek M, Hradilek M, Lepsik M, Konvalinka J, J Med Chem. 2004 Apr 8;47(8):2030-6. PMID:15056001
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