1hgg: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1hgg.gif|left|200px]] | [[Image:1hgg.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1hgg", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_1hgg| PDB=1hgg | SCENE= }} | |||
}} | |||
'''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''' | '''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''' | ||
| Line 33: | Line 30: | ||
[[Category: Skehel, J J.]] | [[Category: Skehel, J J.]] | ||
[[Category: Wiley, D C.]] | [[Category: Wiley, D C.]] | ||
[[Category: | [[Category: Influenza virus hemagglutinin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:49:33 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 18:49, 2 May 2008
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
OverviewOverview
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-->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.
About this StructureAbout this Structure
1HGG is a Single protein structure of sequence from Unidentified influenza virus. Full crystallographic information is available from OCA.
ReferenceReference
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:1327122 Page seeded by OCA on Fri May 2 18:49:33 2008