1qa7: Difference between revisions
New page: left|200px<br /><applet load="1qa7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qa7, resolution 1.9Å" /> '''CRYSTAL COMPLEX OF TH... |
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[[Image:1qa7.jpg|left|200px]]<br /><applet load="1qa7" size=" | [[Image:1qa7.jpg|left|200px]]<br /><applet load="1qa7" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1qa7, resolution 1.9Å" /> | caption="1qa7, resolution 1.9Å" /> | ||
'''CRYSTAL COMPLEX OF THE 3C PROTEINASE FROM HEPATITIS A VIRUS WITH ITS INHIBITOR AND IMPLICATIONS FOR THE POLYPROTEIN PROCESSING IN HAV'''<br /> | '''CRYSTAL COMPLEX OF THE 3C PROTEINASE FROM HEPATITIS A VIRUS WITH ITS INHIBITOR AND IMPLICATIONS FOR THE POLYPROTEIN PROCESSING IN HAV'''<br /> | ||
==Overview== | ==Overview== | ||
The proteolytic processing of the viral polyprotein is an essential step | The proteolytic processing of the viral polyprotein is an essential step during the life cycle of hepatitis A virus (HAV), as it is in all positive-sense, single-stranded RNA viruses of animals. In HAV the 3C proteinase is the only proteolytic activity involved in the polyprotein processing. The specific recognition of the cleavage sites by the 3C proteinase depends on the amino acid sequence of the cleavage site. The structure of the complex of the HAV 3C proteinase and a dipeptide inhibitor has been determined by X-ray crystallography. The double-mutant of HAV 3C (C24S, F82A) was inhibited with the specific inhibitor iodoacetyl-valyl-phenylalanyl-amide. The resulting complex had an acetyl-Val-Phe-amide group covalently attached to the S(gamma) atom of the nucleophilic Cys 172 of the enzyme. Crystals of the complex of HAV 3C (C24S, F82A) acetyl-Val-Phe-amide were found to be monoclinic, space group P2(1), having 4 molecules in the asymmetric unit and diffracting to 1.9-A resolution. The final refined structure consists of 4 molecules of HAV 3C (C24S,F82A) acetyl-Val-Phe-amide, 1 molecule of DMSO, 1 molecule of glycerol, and 514 water molecules. There are considerable conformational differences among the four molecules in the asymmetric unit. The final R-factor is 20.4% for all observed reflections between 15.0- and 1.9-A resolution and the corresponding R(free) is 29.8%. The dipeptide inhibitor is bound to the S(1)(') and S(2)(') specificity subsites of the proteinase. The crystal structure reveals that the HAV 3C proteinase possesses a well-defined S(2)(') specificity pocket and suggests that the P(2)(') residue could be an important determinant for the selection of the primary cleavage site during the polyprotein processing in HAV. | ||
==About this Structure== | ==About this Structure== | ||
1QA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ACE, VAL, NFA, DMS and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1QA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene>, <scene name='pdbligand=VAL:'>VAL</scene>, <scene name='pdbligand=NFA:'>NFA</scene>, <scene name='pdbligand=DMS:'>DMS</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QA7 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: ]] | [[Category: ]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bergmann, E | [[Category: Bergmann, E M.]] | ||
[[Category: Cherney, M | [[Category: Cherney, M M.]] | ||
[[Category: James, M | [[Category: James, M N.G.]] | ||
[[Category: Mckendrick, J.]] | [[Category: Mckendrick, J.]] | ||
[[Category: Vederas, J | [[Category: Vederas, J C.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: DMS]] | [[Category: DMS]] | ||
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[[Category: chymotrypsin-like cysteine proteinase viral protease p'-site inhibitor]] | [[Category: chymotrypsin-like cysteine proteinase viral protease p'-site inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:36 2008'' | ||
Revision as of 15:37, 21 February 2008
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CRYSTAL COMPLEX OF THE 3C PROTEINASE FROM HEPATITIS A VIRUS WITH ITS INHIBITOR AND IMPLICATIONS FOR THE POLYPROTEIN PROCESSING IN HAV
OverviewOverview
The proteolytic processing of the viral polyprotein is an essential step during the life cycle of hepatitis A virus (HAV), as it is in all positive-sense, single-stranded RNA viruses of animals. In HAV the 3C proteinase is the only proteolytic activity involved in the polyprotein processing. The specific recognition of the cleavage sites by the 3C proteinase depends on the amino acid sequence of the cleavage site. The structure of the complex of the HAV 3C proteinase and a dipeptide inhibitor has been determined by X-ray crystallography. The double-mutant of HAV 3C (C24S, F82A) was inhibited with the specific inhibitor iodoacetyl-valyl-phenylalanyl-amide. The resulting complex had an acetyl-Val-Phe-amide group covalently attached to the S(gamma) atom of the nucleophilic Cys 172 of the enzyme. Crystals of the complex of HAV 3C (C24S, F82A) acetyl-Val-Phe-amide were found to be monoclinic, space group P2(1), having 4 molecules in the asymmetric unit and diffracting to 1.9-A resolution. The final refined structure consists of 4 molecules of HAV 3C (C24S,F82A) acetyl-Val-Phe-amide, 1 molecule of DMSO, 1 molecule of glycerol, and 514 water molecules. There are considerable conformational differences among the four molecules in the asymmetric unit. The final R-factor is 20.4% for all observed reflections between 15.0- and 1.9-A resolution and the corresponding R(free) is 29.8%. The dipeptide inhibitor is bound to the S(1)(') and S(2)(') specificity subsites of the proteinase. The crystal structure reveals that the HAV 3C proteinase possesses a well-defined S(2)(') specificity pocket and suggests that the P(2)(') residue could be an important determinant for the selection of the primary cleavage site during the polyprotein processing in HAV.
About this StructureAbout this Structure
1QA7 is a Single protein structure of sequence from [1] with , , , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV., Bergmann EM, Cherney MM, Mckendrick J, Frormann S, Luo C, Malcolm BA, Vederas JC, James MN, Virology. 1999 Dec 5;265(1):153-63. PMID:10603326 [[Category: ]]
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