View source for 7kdo


==Crystal structure of Escherichia coli HPPK in complex with bisubstrate inhibitor HP-73==
<StructureSection load='7kdo' size='340' side='right'caption='[[7kdo]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kdo]] 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=7KDO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KDO 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H73:5-S-[(2R,4R)-1-{2-[(2-amino-7,7-dimethyl-4-oxo-3,4,7,8-tetrahydropteridine-6-carbonyl)amino]ethyl}-2-carboxypiperidin-4-yl]-5-thioadenosine'>H73</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=7kdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kdo OCA], [https://pdbe.org/7kdo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kdo RCSB], [https://www.ebi.ac.uk/pdbsum/7kdo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kdo ProSAT]</span></td></tr>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kdo" style="background-color:#fffaf0;"></div>

==See Also==
*[[HPPK 3D structures|HPPK 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Ji X]]
[[Category: Shaw GX]]
[[Category: Shi G]]