View source for 2q5k

[[Image:2q5k.gif|left|200px]]<br /><applet load="2q5k" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="2q5k, resolution 1.95&Aring;" />
'''Crystal structure of lopinavir bound to wild type HIV-1 protease'''<br />

==Overview==
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric, dipeptide isosteres have been synthesized and evaluated. The inhibitors, were designed by incorporating N-phenyloxazolidinone-5-carboxamides into, the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2, and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a, position proximal to the central hydroxyl group showed low nM inhibitory, activities against wild-type HIV-1 protease. Selected compounds were, further evaluated for their inhibitory activities against a panel of, multidrug-resistant protease variants and for their antiviral potencies in, MT-4 cells. The crystal structures of lopinavir (LPV) and two new, inhibitors containing phenyloxazolidinone-based ligands in complex with, wild-type HIV-1 protease have been determined. A comparison of the, inhibitor-protease structures with the LPV-protease structure provides, valuable insight into the binding mode of the new inhibitors to the, protease enzyme. Based on the crystal structures and knowledge of, structure-activity relationships, new inhibitors can be designed with, enhanced enzyme inhibitory and antiviral potencies.

==About this Structure==
2Q5K 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=PO4:'>PO4</scene> and <scene name='pdbligand=AB1:'>AB1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q5K OCA]. 

==Reference==
Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2' Ligands in Pseudosymmetric Dipeptide Isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17696512 17696512]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Nalam, M.N.L.]]
[[Category: Schiffer, C.A.]]
[[Category: AB1]]
[[Category: PO4]]
[[Category: drug design]]
[[Category: hiv-1 protease]]
[[Category: hydrolase]]
[[Category: protease inhibitors]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:37:36 2008''