2a5a: Difference between revisions
New page: left|200px<br /><applet load="2a5a" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a5a, resolution 2.08Å" /> '''Crystal structure of... |
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[[Image:2a5a.gif|left|200px]]<br /><applet load="2a5a" size=" | [[Image:2a5a.gif|left|200px]]<br /><applet load="2a5a" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2a5a, resolution 2.08Å" /> | caption="2a5a, resolution 2.08Å" /> | ||
'''Crystal structure of unbound SARS coronavirus main peptidase in the space group C2'''<br /> | '''Crystal structure of unbound SARS coronavirus main peptidase in the space group C2'''<br /> | ||
==Overview== | ==Overview== | ||
The main peptidase (M(pro)) from the coronavirus (CoV) causing severe | The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1). | ||
==About this Structure== | ==About this Structure== | ||
2A5A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_sars_coronavirus Human sars coronavirus] with CL and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2A5A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_sars_coronavirus Human sars coronavirus] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Human sars coronavirus]] | [[Category: Human sars coronavirus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cherney, M | [[Category: Cherney, M M.]] | ||
[[Category: Eltis, L | [[Category: Eltis, L D.]] | ||
[[Category: Huitema, C.]] | [[Category: Huitema, C.]] | ||
[[Category: James, K | [[Category: James, K E.]] | ||
[[Category: James, M | [[Category: James, M N.]] | ||
[[Category: Lee, T | [[Category: Lee, T W.]] | ||
[[Category: Liu, J.]] | [[Category: Liu, J.]] | ||
[[Category: Powers, J | [[Category: Powers, J C.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
| Line 33: | Line 33: | ||
[[Category: specificity pockets]] | [[Category: specificity pockets]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:45 2008'' | ||
Revision as of 17:23, 21 February 2008
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Crystal structure of unbound SARS coronavirus main peptidase in the space group C2
OverviewOverview
The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1).
About this StructureAbout this Structure
2A5A is a Single protein structure of sequence from Human sars coronavirus with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide., Lee TW, Cherney MM, Huitema C, Liu J, James KE, Powers JC, Eltis LD, James MN, J Mol Biol. 2005 Nov 11;353(5):1137-51. Epub 2005 Sep 27. PMID:16219322
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