4knv: Difference between revisions
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The | ==The crystal structure of APO HUMAN HDHD4 FROM SE-MAD== | ||
<StructureSection load='4knv' size='340' side='right'caption='[[4knv]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4knv]] is a 2 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=4KNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KNV 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]] 1.993Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4knv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4knv OCA], [https://pdbe.org/4knv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4knv RCSB], [https://www.ebi.ac.uk/pdbsum/4knv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4knv ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The design, synthesis and characterization of a phosphonate inhibitor of N-acetylneuraminate-9-phosphate phosphatase (HDHD4) is described. Compound 3, where the substrate C-9 oxygen was replaced with a nonlabile CH2 group, inhibits HDHD4 with a binding affinity (IC50 11muM) in the range of the native substrate Neu5Ac-9-P (compound 1, Km 47muM). Combined SAR, modeling and NMR studies are consistent with the phosphonate group in inhibitor 3 forming a stable complex with native Mg(2+). In addition to this key interaction, the C-1 carboxylate of the sugar interacts with a cluster of basic residues, K141, R104 and R72. Comparative NMR studies of compounds 3 and 1 with Ca(2+) and Mg(2+) are indicative of a highly dynamic process in the active site for the HDHD4/Mg(2+)/3 complex. Possible explanations for this observation are discussed. | |||
Design, synthesis, functional and structural characterization of an inhibitor of N-acetylneuraminate-9-phosphate phosphatase: Observation of extensive dynamics in an enzyme/inhibitor complex.,Kim SH, Constantine KL, Duke GJ, Goldfarb V, Hunt JT, Johnson S, Kish K, Klei HE, McDonnell PA, Metzler WJ, Mueller L, Poss MA, Fairchild CR, Bhide RS Bioorg Med Chem Lett. 2013 Jul 15;23(14):4107-11. doi:, 10.1016/j.bmcl.2013.05.052. Epub 2013 May 23. PMID:23747226<ref>PMID:23747226</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4knv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Klei HE]] | |||
Latest revision as of 03:09, 21 November 2024
The crystal structure of APO HUMAN HDHD4 FROM SE-MAD
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