1sip
From Proteopedia
(New page: 200px<br /><applet load="1sip" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sip, resolution 2.3Å" /> '''ALTERNATIVE NATIVE FL...) |
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| - | [[Image:1sip.gif|left|200px]]<br /><applet load="1sip" size=" | + | [[Image:1sip.gif|left|200px]]<br /><applet load="1sip" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sip, resolution 2.3Å" /> | caption="1sip, resolution 2.3Å" /> | ||
'''ALTERNATIVE NATIVE FLAP CONFORMATION REVEALED BY 2.3 ANGSTROMS RESOLUTION STRUCTURE OF SIV PROTEINASE'''<br /> | '''ALTERNATIVE NATIVE FLAP CONFORMATION REVEALED BY 2.3 ANGSTROMS RESOLUTION STRUCTURE OF SIV PROTEINASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A large conformational change is observed between HIV-1 proteinase in the | + | 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== | ==About this Structure== | ||
| - | 1SIP 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:// | + | 1SIP 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== | ==Reference== | ||
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[[Category: Simian immunodeficiency virus]] | [[Category: Simian immunodeficiency virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Wilderspin, A | + | [[Category: Wilderspin, A F.]] |
[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:53 2008'' |
Revision as of 13:01, 21 February 2008
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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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