1hge

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[[Image:1hge.gif|left|200px]]
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==Overview==
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{{ABSTRACT_1327122}}
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The interaction between influenza virus hemagglutinin and its cell-surface receptor, 5-N-acetylneuraminic acid (sialic acid), was probed by the synthesis of 12 sialic acid analogs, including derivatives at the 2-carboxylate, 5-acetamido, 4-, 7-, and 9-hydroxyl, and glycosidic positions. The equilibrium dissociation constants of these analogs were determined by nuclear magnetic resonance spectroscopy. Ligand modifications that reduced or abolished binding included the replacement of the 2-carboxylate with a carboxamide, the substitution of azido or N-benzyloxycarbonyl groups for the 5-acetamido group, and the replacement of the 9-hydroxyl with amino or O-acetyl moieties. Modifications having little effect on binding included the introduction of longer chains at the 4-hydroxyl position, the replacement of the acetamido methyl group with an ethyl group, and the removal of the 7-hydroxyl group. X-ray diffraction studies yielded 3 A resolution crystal structures of hemagglutinin in complex with four of the synthetic analogs [alpha-2-O-methyl-, 4-O-acetyl-alpha-2-O-methyl-, 9-amino-9-deoxy-alpha-2-O-methyl-, and alpha-2-O-(4'-benzylamidocarboxybutyl)-N-acetylneuraminic acid] and with the naturally occurring cell-surface saccharide (alpha 2-3)sialyllactose. The X-ray studies unambiguously establish the position and orientation of bound sialic acid, indicate the position of the lactose group of (alpha 2-3)sialyllactose, and suggest the location of an alpha-glycosidic chain (4'-benzylamidocarboxybutyl) that increases the binding affinity of sialic acid by a factor of about 3. Although the protein complexed with alpha-2-O-methylsialic acid contains the mutation Gly-135--&gt;Arg near the ligand binding site, the mutation apparently does not affect the ligand's position. The X-ray studies allow us to interpret the binding affinities in terms of the crystallographic structure. The results suggest further experiments which could lead to the design of tight binding inhibitors of possible therapeutic value.
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==About this Structure==
==About this Structure==
1HGE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. The following page contains interesting information on the relation of 1HGE with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb76_1.html Hemagglutinin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HGE OCA].
1HGE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. The following page contains interesting information on the relation of 1HGE with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb76_1.html Hemagglutinin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HGE OCA].
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==Reference==
 
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Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography., Sauter NK, Hanson JE, Glick GD, Brown JH, Crowther RL, Park SJ, Skehel JJ, Wiley DC, Biochemistry. 1992 Oct 13;31(40):9609-21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1327122 1327122]
 
[[Category: Hemagglutinin]]
[[Category: Hemagglutinin]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Wiley, D C.]]
[[Category: Wiley, D C.]]
[[Category: Influenza virus hemagglutinin]]
[[Category: Influenza virus hemagglutinin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:49:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:28:01 2008''

Revision as of 14:28, 26 June 2008

Image:1hge.png

Template:STRUCTURE 1hge

BINDING OF INFLUENZA VIRUS HEMAGGLUTININ TO ANALOGS OF ITS CELL-SURFACE RECEPTOR, SIALIC ACID: ANALYSIS BY PROTON NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY


Template:ABSTRACT 1327122

About this Structure

1HGE is a Single protein structure of sequence from Unidentified influenza virus. The following page contains interesting information on the relation of 1HGE with [Hemagglutinin]. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 17:28:01 2008

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