2a5i: Difference between revisions
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New page: left|200px<br /><applet load="2a5i" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a5i, resolution 1.88Å" /> '''Crystal structures o... |
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[[Image:2a5i.gif|left|200px]]<br /><applet load="2a5i" size=" | [[Image:2a5i.gif|left|200px]]<br /><applet load="2a5i" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2a5i, resolution 1.88Å" /> | caption="2a5i, resolution 1.88Å" /> | ||
'''Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide in the space group C2'''<br /> | '''Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide 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== | ||
2A5I 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 AZP, EDO and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2A5I 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=AZP:'>AZP</scene>, <scene name='pdbligand=EDO:'>EDO</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=2A5I 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: AZP]] | [[Category: AZP]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
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[[Category: substrate-like inhibitor]] | [[Category: substrate-like inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:48 2008'' | ||
