View source for 1b9v


==NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN TEH ACTIVE SITE==
<StructureSection load='1b9v' size='340' side='right'caption='[[1b9v]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B9V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B9V FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RA2:1-[4-CARBOXY-2-(3-PENTYLAMINO)PHENYL]-5,5-DI(HYDROXYMETHYL)PYRROLIDIN-2-ONE'>RA2</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1b9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b9v OCA], [https://pdbe.org/1b9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b9v RCSB], [https://www.ebi.ac.uk/pdbsum/1b9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b9v ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The active site of type A or B influenza virus neuraminidase is composed of 11 conserved residues that directly interact with the substrate, sialic acid. An aromatic benzene ring has been used to replace the pyranose of sialic acid in our design of novel neuraminidase inhibitors. A bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the N-acetyl group on the sialic acid. The hydroxymethyl groups replace two active site water molecules, which resulted in the high affinity of the nanomolar inhibitors. However, these inhibitors have greater potency for type A influenza virus than for type B influenza virus. To resolve the differences, we determined the X-ray crystal structure of three benzoic acid substituted inhibitors bound to the active site of B/Lee/40 neuraminidase. The investigation of a hydrophobic aliphatic group and a hydrophilic guanidino group on the aromatic inhibitors shows changes in the interaction with the active site residue Glu275. The results provide an explanation for the difference in efficacy of these inhibitors against types A and B viruses, even though the 11 active site residues of the neuraminidase are conserved.

Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site.,Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:10547289<ref>PMID:10547289</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1b9v" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Air GM]]
[[Category: Atigadda VR]]
[[Category: Brouillette WJ]]
[[Category: Duarte F]]
[[Category: Finley JB]]
[[Category: Luo M]]
[[Category: Zahao JJ]]