1nsc
From Proteopedia
(New page: 200px<br /><applet load="1nsc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nsc, resolution 1.7Å" /> '''INFLUENZA B VIRUS NEU...) |
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| - | [[Image:1nsc.gif|left|200px]]<br /><applet load="1nsc" size=" | + | [[Image:1nsc.gif|left|200px]]<br /><applet load="1nsc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nsc, resolution 1.7Å" /> | caption="1nsc, resolution 1.7Å" /> | ||
'''INFLUENZA B VIRUS NEURAMINIDASE CAN SYNTHESIZE ITS OWN INHIBITOR'''<br /> | '''INFLUENZA B VIRUS NEURAMINIDASE CAN SYNTHESIZE ITS OWN INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Neuraminidase, one of the two surface glycoproteins of | + | BACKGROUND: Neuraminidase, one of the two surface glycoproteins of influenza virus, cleaves terminal sialic acid residues from glycolipids or glycoproteins. Its crystal structure is known at high resolution, but the mechanism of glycosyl hydrolysis remains unclear. RESULTS: We have determined the crystal structure at 1.8 A resolution of two complexes of influenza B/Beijing neuraminidase containing either the reaction product, sialic acid, or the transition state analogue inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). The sialic acid is bound in a distorted 'boat' conformation closely resembling that of bound DANA, stabilized by a conserved tyrosine residue (Tyr408). This distortion also gives rise to a suicidal side reaction that converts sialic acid to DANA at a low rate. CONCLUSIONS: The mechanism of neuraminidase action is distinct from that of other known glycosyl hydrolases. Substrate distortion appears to be the driving force in glycosyl bond hydrolysis and the proton required for catalysis can probably be donated by water, rather than by residues in the active site, thus allowing the enzyme to operate at high pH. The side reaction converting sialic acid to DANA appears reasonably favourable, and it is unclear how this is minimized by the enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 1NSC 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 NAG, SIA and CA as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1NSC 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=NAG:'>NAG</scene>, <scene name='pdbligand=SIA:'>SIA</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1NSC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Influenza b virus]] | [[Category: Influenza b virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Burmeister, W | + | [[Category: Burmeister, W P.]] |
[[Category: Cusack, S.]] | [[Category: Cusack, S.]] | ||
| - | [[Category: Ruigrok, R | + | [[Category: Ruigrok, R W.H.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: hydrolase(o-glycosyl)]] | [[Category: hydrolase(o-glycosyl)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:09:27 2008'' |
Revision as of 12:09, 21 February 2008
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INFLUENZA B VIRUS NEURAMINIDASE CAN SYNTHESIZE ITS OWN INHIBITOR
Overview
BACKGROUND: Neuraminidase, one of the two surface glycoproteins of influenza virus, cleaves terminal sialic acid residues from glycolipids or glycoproteins. Its crystal structure is known at high resolution, but the mechanism of glycosyl hydrolysis remains unclear. RESULTS: We have determined the crystal structure at 1.8 A resolution of two complexes of influenza B/Beijing neuraminidase containing either the reaction product, sialic acid, or the transition state analogue inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). The sialic acid is bound in a distorted 'boat' conformation closely resembling that of bound DANA, stabilized by a conserved tyrosine residue (Tyr408). This distortion also gives rise to a suicidal side reaction that converts sialic acid to DANA at a low rate. CONCLUSIONS: The mechanism of neuraminidase action is distinct from that of other known glycosyl hydrolases. Substrate distortion appears to be the driving force in glycosyl bond hydrolysis and the proton required for catalysis can probably be donated by water, rather than by residues in the active site, thus allowing the enzyme to operate at high pH. The side reaction converting sialic acid to DANA appears reasonably favourable, and it is unclear how this is minimized by the enzyme.
About this Structure
1NSC is a Single protein structure of sequence from Influenza b virus with , and as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
Reference
Influenza B virus neuraminidase can synthesize its own inhibitor., Burmeister WP, Henrissat B, Bosso C, Cusack S, Ruigrok RW, Structure. 1993 Sep 15;1(1):19-26. PMID:8069621
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