1hvh
From Proteopedia
(New page: 200px<br /> <applet load="1hvh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hvh, resolution 1.8Å" /> '''NONPEPTIDE CYCLIC CY...) |
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| - | [[Image:1hvh.gif|left|200px]]<br /> | + | [[Image:1hvh.gif|left|200px]]<br /><applet load="1hvh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hvh" size=" | + | |
caption="1hvh, resolution 1.8Å" /> | caption="1hvh, resolution 1.8Å" /> | ||
'''NONPEPTIDE CYCLIC CYANOGUANIDINES AS HIV PROTEASE INHIBITORS'''<br /> | '''NONPEPTIDE CYCLIC CYANOGUANIDINES AS HIV PROTEASE INHIBITORS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Comparison of the high-resolution X-ray structures of the native HIV-1 | + | Comparison of the high-resolution X-ray structures of the native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible. The movement at the tip of the flaps could be as large as 7 A. On the basis of this observation, cyclic cyanoguanidines have been designed, synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The choice of cyclic cyanoguanidines over cyclic guanidines was based on the reduced basicity of the former. X-ray structure studies of the HIV PR complex with cyclic cyanoguanidine demonstrated that in analogy to cyclic urea, cyclic cyanoguanidines also displace the unique structural water molecule. The structure-activity relationship of the cyclic cyanoguanidines is compared with that of the corresponding cyclic urea analogues. The differences in binding constants of the two series of compounds have been rationalized using high-resolution X-ray structure information. |
==About this Structure== | ==About this Structure== | ||
| - | 1HVH 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 Q82 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:// | + | 1HVH 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=Q82:'>Q82</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=1HVH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chang, C | + | [[Category: Chang, C H.]] |
[[Category: Q82]] | [[Category: Q82]] | ||
[[Category: acid protease]] | [[Category: acid protease]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:16 2008'' |
Revision as of 11:05, 21 February 2008
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NONPEPTIDE CYCLIC CYANOGUANIDINES AS HIV PROTEASE INHIBITORS
Overview
Comparison of the high-resolution X-ray structures of the native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible. The movement at the tip of the flaps could be as large as 7 A. On the basis of this observation, cyclic cyanoguanidines have been designed, synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The choice of cyclic cyanoguanidines over cyclic guanidines was based on the reduced basicity of the former. X-ray structure studies of the HIV PR complex with cyclic cyanoguanidine demonstrated that in analogy to cyclic urea, cyclic cyanoguanidines also displace the unique structural water molecule. The structure-activity relationship of the cyclic cyanoguanidines is compared with that of the corresponding cyclic urea analogues. The differences in binding constants of the two series of compounds have been rationalized using high-resolution X-ray structure information.
About this Structure
1HVH 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
Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies., Jadhav PK, Woerner FJ, Lam PY, Hodge CN, Eyermann CJ, Man HW, Daneker WF, Bacheler LT, Rayner MM, Meek JL, Erickson-Viitanen S, Jackson DA, Calabrese JC, Schadt M, Chang CH, J Med Chem. 1998 Apr 23;41(9):1446-55. PMID:9554878
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