7kdr: Difference between revisions
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==Crystal structure of Escherichia coli HPPK in complex with bisubstrate inhibitor HP-75== | ==Crystal structure of Escherichia coli HPPK in complex with bisubstrate inhibitor HP-75== | ||
<StructureSection load='7kdr' size='340' side='right'caption='[[7kdr]]' scene=''> | <StructureSection load='7kdr' size='340' side='right'caption='[[7kdr]], [[Resolution|resolution]] 1.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KDR OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7kdr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KDR FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.488Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=J1L:5-{[(2R,4R)-1-{2-[(2-amino-7,7-dimethyl-4-oxo-3,4,7,8-tetrahydropteridine-6-carbonyl)amino]ethyl}-2-carboxypiperidin-4-yl]sulfonyl}-5-deoxyadenosine'>J1L</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=7kdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kdr OCA], [https://pdbe.org/7kdr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kdr RCSB], [https://www.ebi.ac.uk/pdbsum/7kdr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kdr ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/HPPK_ECOLI HPPK_ECOLI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate biosynthesis pathway. It catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). HPPK is essential for microorganisms but absent in mammals; therefore, it is an attractive target for developing novel antimicrobial agents. Previously, based on our studies of the structure and mechanism of HPPK, we created first-generation bisubstrate inhibitors by linking 6-hydroxymethylpterin to adenosine through phosphate groups, and developed second-generation inhibitors by replacing the phosphate bridge with a linkage that contains a piperidine moiety. Here, we report third-generation inhibitors designed based on the piperidine-containing inhibitor, mimicking the transition state. We synthesized two such inhibitors, characterized their protein-binding and enzyme inhibition properties, and determined their crystal structures in complex with HPPK, advancing the development of such bisubstrate analog inhibitors. | |||
Bisubstrate inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Transition state analogs for high affinity binding.,Shi G, Shaw GX, Zhu F, Tarasov SG, Ji X Bioorg Med Chem. 2021 Jan 1;29:115847. doi: 10.1016/j.bmc.2020.115847. Epub 2020 , Nov 9. PMID:33199204<ref>PMID:33199204</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7kdr" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[HPPK 3D structures|HPPK 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ji X]] | [[Category: Ji X]] | ||
[[Category: Shaw GX]] | [[Category: Shaw GX]] | ||
[[Category: Shi G]] | [[Category: Shi G]] | ||