1vcj
From Proteopedia
(New page: 200px<br /><applet load="1vcj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vcj, resolution 2.40Å" /> '''Influenza B virus ne...) |
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| - | [[Image:1vcj.gif|left|200px]]<br /><applet load="1vcj" size=" | + | [[Image:1vcj.gif|left|200px]]<br /><applet load="1vcj" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1vcj, resolution 2.40Å" /> | caption="1vcj, resolution 2.40Å" /> | ||
'''Influenza B virus neuraminidase complexed with 1-(4-Carboxy-2-(3-pentylamino)phenyl)-5-aminomethyl-5-hydroxymethyl-pyrrolidin-2-one'''<br /> | '''Influenza B virus neuraminidase complexed with 1-(4-Carboxy-2-(3-pentylamino)phenyl)-5-aminomethyl-5-hydroxymethyl-pyrrolidin-2-one'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Owing to the highly conserved nature of its active site, Influenza B virus | + | Owing to the highly conserved nature of its active site, Influenza B virus neuraminidase (NA) has emerged as a major target for the design of novel anti-influenza drugs. A benzene-ring scaffold has been used in place of the pyranose ring of sialic acid to develop simpler NA inhibitors that contain a minimal number of chiral centers. A new compound belonging to this series, BANA 207, showed significant improvement in inhibitory activity against Influenza B virus NA compared with its parent compound. Here, the structural analysis of a complex of BANA 207 with influenza virus B/Lee/40 NA is reported. The results indicate that BANA 207 forms an unexpected interaction with the crucial active-site residue Glu275 that stabilizes the side chain of this residue in a conformation previously unobserved in NA-inhibitor complexes. This change in the side-chain orientation of Glu275 alters the topology of the triglycerol pocket, which accommodates an additional lipophilic substitution at the benzene ring and may provide an explanation for the increased activity of BANA 207 against Influenza B virus NA. |
==About this Structure== | ==About this Structure== | ||
| - | 1VCJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus Influenza b virus] with IBA as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 1VCJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus Influenza b virus] with <scene name='pdbligand=IBA:'>IBA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1UJA. Active as [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VCJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Influenza b virus]] | [[Category: Influenza b virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Air, G | + | [[Category: Air, G M.]] |
| - | [[Category: Ali, S | + | [[Category: Ali, S M.]] |
| - | [[Category: Bajpai, S | + | [[Category: Bajpai, S N.]] |
| - | [[Category: Brouillette, W | + | [[Category: Brouillette, W J.]] |
| - | [[Category: Lommer, B | + | [[Category: Lommer, B S.]] |
[[Category: Luo, M.]] | [[Category: Luo, M.]] | ||
[[Category: IBA]] | [[Category: IBA]] | ||
| Line 26: | Line 26: | ||
[[Category: small molecule inhibitor]] | [[Category: small molecule inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:33:48 2008'' |
Revision as of 13:33, 21 February 2008
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Influenza B virus neuraminidase complexed with 1-(4-Carboxy-2-(3-pentylamino)phenyl)-5-aminomethyl-5-hydroxymethyl-pyrrolidin-2-one
Overview
Owing to the highly conserved nature of its active site, Influenza B virus neuraminidase (NA) has emerged as a major target for the design of novel anti-influenza drugs. A benzene-ring scaffold has been used in place of the pyranose ring of sialic acid to develop simpler NA inhibitors that contain a minimal number of chiral centers. A new compound belonging to this series, BANA 207, showed significant improvement in inhibitory activity against Influenza B virus NA compared with its parent compound. Here, the structural analysis of a complex of BANA 207 with influenza virus B/Lee/40 NA is reported. The results indicate that BANA 207 forms an unexpected interaction with the crucial active-site residue Glu275 that stabilizes the side chain of this residue in a conformation previously unobserved in NA-inhibitor complexes. This change in the side-chain orientation of Glu275 alters the topology of the triglycerol pocket, which accommodates an additional lipophilic substitution at the benzene ring and may provide an explanation for the increased activity of BANA 207 against Influenza B virus NA.
About this Structure
1VCJ is a Single protein structure of sequence from Influenza b virus with as ligand. This structure supersedes the now removed PDB entry 1UJA. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
Reference
A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase., Lommer BS, Ali SM, Bajpai SN, Brouillette WJ, Air GM, Luo M, Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1017-23. Epub 2004, May 21. PMID:15159560
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