View source for 8jnv


==PfDXR - Mn2+ - MAMK89 ternary complex==
<StructureSection load='8jnv' size='340' side='right'caption='[[8jnv]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jnv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_HB3 Plasmodium falciparum HB3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JNV 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UW0:[(1~{S})-4-oxidanylidene-4-[oxidanyl(3-phenylpropyl)amino]-1-phenyl-butyl]phosphonic+acid'>UW0</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=8jnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jnv OCA], [https://pdbe.org/8jnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jnv RCSB], [https://www.ebi.ac.uk/pdbsum/8jnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jnv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DXR_PLAFX DXR_PLAFX] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).<ref>PMID:10477522</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Reverse analogs of the phosphonohydroxamic acid antibiotic fosmidomycin are potent inhibitors of the nonmevalonate isoprenoid biosynthesis enzyme 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR, IspC) of Plasmodium falciparum. Some novel analogs with large phenylalkyl substituents at the hydroxamic acid nitrogen exhibit nanomolar PfDXR inhibition and potent in vitro growth inhibition of P. falciparum parasites coupled with good parasite selectivity. X-ray crystallographic studies demonstrated that the N-phenylpropyl substituent of the newly developed lead compound 13e is accommodated in a subpocket within the DXR catalytic domain but does not reach the NADPH binding pocket of the N-terminal domain. As shown for reverse carba and thia analogs, PfDXR selectively binds the S-enantiomer of the new lead compound. In addition, some representatives of the novel inhibitor subclass are nanomolar Escherichia coli DXR inhibitors, whereas the inhibition of Mycobacterium tuberculosis DXR is considerably weaker.

Reverse N-Substituted Hydroxamic Acid Derivatives of Fosmidomycin Target a Previously Unknown Subpocket of 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase (DXR).,Abdullaziz MA, Takada S, Illarionov B, Pessanha de Carvalho L, Sakamoto Y, Hofmann S, Knak T, Kiffe-Delf AL, Mazzone F, Pfeffer K, Kalscheuer R, Bacher A, Held J, Fischer M, Tanaka N, Kurz T ACS Infect Dis. 2024 May 10;10(5):1739-1752. doi: 10.1021/acsinfecdis.4c00100. , Epub 2024 Apr 22. PMID:38647213<ref>PMID:38647213</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jnv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum HB3]]
[[Category: Sakamoto Y]]
[[Category: Takada S]]
[[Category: Tanaka N]]