4ncs: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ncs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCS FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ncs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSR:(2S,3S,4R,5R,6R)-5-ACETAMIDO-2,3-BIS(FLUORANYL)-4-OXIDANYL-6-[(1S,2S)-1,2,3-TRIS(OXIDANYL)PROPYL]OXANE-2-CARBOXYLIC+ACID'>FSR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.201Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSR:(2S,3S,4R,5R,6R)-5-ACETAMIDO-2,3-BIS(FLUORANYL)-4-OXIDANYL-6-[(1S,2S)-1,2,3-TRIS(OXIDANYL)PROPYL]OXANE-2-CARBOXYLIC+ACID'>FSR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4ncs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncs OCA], [https://pdbe.org/4ncs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncs RCSB], [https://www.ebi.ac.uk/pdbsum/4ncs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncs ProSAT]</span></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=4ncs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncs OCA], [https://pdbe.org/4ncs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncs RCSB], [https://www.ebi.ac.uk/pdbsum/4ncs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 19:53, 20 September 2023
Human sialidase 2 in complex with 2,3-difluorosialic acid (covalent intermediate)Human sialidase 2 in complex with 2,3-difluorosialic acid (covalent intermediate)
Structural highlights
FunctionNEUR2_HUMAN Hydrolyzes sialylated compounds. Publication Abstract from PubMed3-Fluorosialosyl fluorides are inhibitors of sialidases that function by the formation of a long-lived covalent active-site adduct and have potential as therapeutics if made specific for the pathogen sialidase. Surprisingly, human Neu2 and the Trypanosoma cruzi trans-sialidase are inactivated more rapidly by the reagent with an equatorial fluorine at C3 than by its axial epimer, with reactivation following the same pattern. To explore a possible stereoelectronic basis for this, rate constants for spontaneous hydrolysis of the full series of four 3-fluorosialosyl fluorides were measured, and ground-state energies for each computed. The alpha (equatorial) anomeric fluorides hydrolyze more rapidly than their beta anomers, consistent with their higher ground-state energies. However ground-state energies do not explain the relative spontaneous reactivities of the 3-fluoro-epimers. The three-dimensional structures of the two 3-fluoro-sialosyl enzyme intermediates of human Neu2 were solved, revealing key stabilizing interactions between Arg21 and the equatorial, but not the axial, fluorine. Because of changes in geometry these interactions will increase at the transition state, likely explaining the difference in reaction rates. Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural insights.,Buchini S, Gallat FX, Greig IR, Kim JH, Wakatsuki S, Chavas LM, Withers SG Angew Chem Int Ed Engl. 2014 Mar 24;53(13):3382-6. doi: 10.1002/anie.201309675., Epub 2014 Mar 3. PMID:24591206[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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