View source for 3anl


==Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with pyridin-2-ylmethylphosphonic acid==
<StructureSection load='3anl' size='340' side='right'caption='[[3anl]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3anl]] is a 2 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=3ANL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ANL 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SYC:(PYRIDIN-2-YLMETHYL)PHOSPHONIC+ACID'>SYC</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=3anl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3anl OCA], [https://pdbe.org/3anl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3anl RCSB], [https://www.ebi.ac.uk/pdbsum/3anl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3anl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DXR_ECOLI DXR_ECOLI] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).[HAMAP-Rule:MF_00183]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fosmidomycin, a potent inhibitor of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), has antibacterial and antimalaria activity. Due to its poor pharmacokinetics, more lipophilic DXR inhibitors are needed. However, the hydrophobic binding site(s) in DXR remains elusive. Here, pyridine/quinoline containing phosphonates are identified to be DXR inhibitors with IC(50) values as low as 840 nM. We also report three DXR:inhibitor structures, revealing a novel binding mode. The indole group of Trp211 is found to move ~4.6 A to open up a mainly hydrophobic pocket, where the pyridine/quinoline rings of the inhibitors are located and have strong pi-pi stacking/charge-transfer interactions with the indole. Docking studies demonstrate our structures could be used to predict the binding modes of other lipophilic DXR inhibitors. Overall, this work shows an important role of Trp211 in inhibitor recognition and provides a structural basis for future drug design and development.

Structures of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase/Lipophilic Phosphonate Complexes.,Deng L, Endo K, Kato M, Cheng G, Yajima S, Song Y ACS Med Chem Lett. 2011 Feb 10;2(2):165-170. PMID:21379374<ref>PMID:21379374</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3anl" style="background-color:#fffaf0;"></div>

==See Also==
*[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Deng L]]
[[Category: Endo K]]
[[Category: Kato M]]
[[Category: Song Y]]
[[Category: Yajima S]]