1sip

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Categories: Simian immunodeficiency virus | Single protein | Wilderspin, A F. | Hydrolase(acid proteinase)

Revision as of 13:01, 21 February 2008

ALTERNATIVE NATIVE FLAP CONFORMATION REVEALED BY 2.3 ANGSTROMS RESOLUTION STRUCTURE OF SIV PROTEINASE

Overview

A large conformational change is observed between HIV-1 proteinase in the ligand-free state and in complexes with transition-state inhibitors. Crystal structures of this enzyme have either the flaps open for the native or ligand-free enzyme or the flaps closed for peptidomimetic ligand-bound enzyme. We describe the structure of native recombinant SIV proteinase which like other retroviral proteinases crystallizes as a perfect 2-fold symmetric dimer but in a different crystal packing arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the ligand-free state adopts the closed flaps conformation, demonstrating that ligand binding is not a prerequisite for the closed flaps conformation. The catalytic water was clearly observed between the two aspartates which were not perfectly co-planar, and in this structure the active site cleft is more restricted than for either inhibitor bound or ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains in the simian enzyme core has resulted in a more exposed N terminus than for HIV-1 PR which we predict could enhance autocatalytic cleavage at the N terminus.

About this Structure

1SIP is a Single protein structure of sequence from Simian immunodeficiency virus. Full crystallographic information is available from OCA.

Reference

Alternative native flap conformation revealed by 2.3 A resolution structure of SIV proteinase., Wilderspin AF, Sugrue RJ, J Mol Biol. 1994 May 27;239(1):97-103. PMID:8196050

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-[[Image:1sip.gif|left|200px]]<br /><applet load="1sip" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1sip.gif|left|200px]]<br /><applet load="1sip" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1sip, resolution 2.3&Aring;" />
 '''ALTERNATIVE NATIVE FLAP CONFORMATION REVEALED BY 2.3 ANGSTROMS RESOLUTION STRUCTURE OF SIV PROTEINASE'''<br />
 ==Overview==
-A large conformational change is observed between HIV-1 proteinase in the, ligand-free state and in complexes with transition-state inhibitors., Crystal structures of this enzyme have either the flaps open for the, native or ligand-free enzyme or the flaps closed for peptidomimetic, ligand-bound enzyme. We describe the structure of native recombinant SIV, proteinase which like other retroviral proteinases crystallizes as a, perfect 2-fold symmetric dimer but in a different crystal packing, arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the, ligand-free state adopts the closed flaps conformation, demonstrating that, ligand binding is not a prerequisite for the closed flaps conformation., The catalytic water was clearly observed between the two aspartates which, were not perfectly co-planar, and in this structure the active site cleft, is more restricted than for either inhibitor bound or ligand-free HIV-1, proteinase. Accommodation of two bulkier side-chains in the simian enzyme, core has resulted in a more exposed N terminus than for HIV-1 PR which we, predict could enhance autocatalytic cleavage at the N terminus.
+A large conformational change is observed between HIV-1 proteinase in the ligand-free state and in complexes with transition-state inhibitors. Crystal structures of this enzyme have either the flaps open for the native or ligand-free enzyme or the flaps closed for peptidomimetic ligand-bound enzyme. We describe the structure of native recombinant SIV proteinase which like other retroviral proteinases crystallizes as a perfect 2-fold symmetric dimer but in a different crystal packing arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the ligand-free state adopts the closed flaps conformation, demonstrating that ligand binding is not a prerequisite for the closed flaps conformation. The catalytic water was clearly observed between the two aspartates which were not perfectly co-planar, and in this structure the active site cleft is more restricted than for either inhibitor bound or ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains in the simian enzyme core has resulted in a more exposed N terminus than for HIV-1 PR which we predict could enhance autocatalytic cleavage at the N terminus.
 ==About this Structure==
-SIP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SIP OCA].
+SIP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SIP OCA].
 ==Reference==
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 [[Category: Simian immunodeficiency virus]]
 [[Category: Single protein]]
-[[Category: Wilderspin, A.F.]]
+[[Category: Wilderspin, A F.]]
 [[Category: hydrolase(acid proteinase)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 00:35:13 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:53 2008''