View source for 4yiw


==DIHYDROOROTASE FROM BACILLUS ANTHRACIS WITH SUBSTRATE BOUND==
<StructureSection load='4yiw' size='340' side='right'caption='[[4yiw]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yiw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YIW 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCD:N-CARBAMOYL-L-ASPARTATE'>NCD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4yiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yiw OCA], [https://pdbe.org/4yiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yiw RCSB], [https://www.ebi.ac.uk/pdbsum/4yiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yiw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PYRC_BACAN PYRC_BACAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases. Despite the differences in the catalytic loop, the structure confirms that the key interactions between the substrate and active site residues are similar between Class I and Class II DHOase enzymes, which we further validated by mutagenesis studies. B. anthracis DHOase is also a potential antibacterial drug target. In order to identify prospective inhibitors, we performed high-throughput screening against several libraries using a colorimetric enzymatic assay and an orthogonal fluorescence thermal binding assay. Surface plasmon resonance was used for determining binding affinity (KD) and competition analysis with Ca-asp. Our results highlight that the primary difference between Class I and Class II DHOase is the catalytic loop. We also identify several compounds that can potentially be further optimized as potential B. anthracis inhibitors.

Ca-asp bound X-ray structure and inhibition of Bacillus anthracis dihydroorotase (DHOase).,Rice AJ, Lei H, Santarsiero BD, Lee H, Johnson ME Bioorg Med Chem. 2016 Oct 1;24(19):4536-43. doi: 10.1016/j.bmc.2016.07.055. Epub , 2016 Jul 29. PMID:27499369<ref>PMID:27499369</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yiw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydroorotase 3D structures|Dihydroorotase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Large Structures]]
[[Category: Johnson ME]]
[[Category: Lee H]]
[[Category: Lei H]]
[[Category: Rice AJ]]
[[Category: Santarsiero BD]]