View source for 2nph

[[Image:2nph.gif|left|200px]]<br />
<applet load="2nph" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2nph, resolution 1.650&Aring;" />
'''Crystal structure of HIV1 protease in situ product complex'''<br />

==Overview==
HIV-1 protease is an effective target for designing drugs against AIDS, and structural information about the true transition state and the correct, mechanism can provide important inputs. We present here the, three-dimensional structure of a bi-product complex between HIV-1 protease, and the two cleavage product peptides AETF and YVDGAA. The structure, refined against synchrotron data to 1.65 A resolution, shows the, occurrence of the cleavage reaction in the crystal, with the product, peptides still held in the enzyme active site. The separation between the, scissile carbon and nitrogen atoms is 2.67 A, which is shorter than a, normal van der Waal separation, but it is much longer than a peptide bond, length. The substrate is thus in a stage just past the G'Z intermediate, described in Northrop's mechanism [Northrop DB (2001) Acc Chem Res, 34:790-797]. Because the products are generated in situ, the structure, by, extrapolation, can give insight into the mechanism of the cleavage, reaction. Both oxygens of the generated carboxyl group form hydrogen bonds, with atoms at the catalytic center: one to the OD2 atom of a catalytic, aspartate and the other to the scissile nitrogen atom. The latter hydrogen, bond may have mediated protonation of scissile nitrogen, triggering, peptide bond cleavage. The inner oxygen atoms of the catalytic aspartates, in the complex are 2.30 A apart, indicating a low-barrier hydrogen bond, between them at this stage of the reaction, an observation not included in, Northrop's proposal. This structure forms a template for designing, mechanism-based inhibitors.

==About this Structure==
2NPH 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]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2NPH OCA]. 

==Reference==
Crystal structure of HIV-1 protease in situ product complex and observation of a low-barrier hydrogen bond between catalytic aspartates., Das A, Prashar V, Mahale S, Serre L, Ferrer JL, Hosur MV, Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18464-9. Epub 2006 Nov 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17116869 17116869]
[[Category: HIV-1 retropepsin]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Das, A.]]
[[Category: Hosur, M.V.]]
[[Category: Prashar, V.]]
[[Category: anti-parallel beta sheet]]

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