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==Crystal Structure of Bacillus anthracis Inosine Monophosphate Dehydrogenase in the complex with IMP==
<StructureSection load='3usb' size='340' side='right'caption='[[3usb]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3usb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Ames Bacillus anthracis str. Ames]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3USB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3USB 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]] 2.38&#8491;</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3usb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3usb OCA], [https://pdbe.org/3usb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3usb RCSB], [https://www.ebi.ac.uk/pdbsum/3usb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3usb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A6L8P2U9_BACAN A0A6L8P2U9_BACAN] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]
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== Publication Abstract from PubMed ==
Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first unique step of the GMP branch of the purine nucleotide biosynthetic pathway. This enzyme is found in organisms of all three kingdoms. IMPDH inhibitors have broad clinical applications in cancer treatment, as antiviral drugs and as immunosuppressants, and have also displayed antibiotic activity. We have determined three crystal structures of Bacillus anthracis IMPDH, in a phosphate ion-bound (termed "apo") form and in complex with its substrate, inosine 5'-monophosphate (IMP), and product, xanthosine 5'-monophosphate (XMP). This is the first example of a bacterial IMPDH in more than one state from the same organism. Furthermore, for the first time for a prokaryotic enzyme, the entire active site flap, containing the conserved Arg-Tyr dyad, is clearly visible in the structure of the apoenzyme. Kinetic parameters for the enzymatic reaction were also determined, and the inhibitory effect of XMP and mycophenolic acid (MPA) has been studied. In addition, the inhibitory potential of two known Cryptosporidium parvum IMPDH inhibitors was examined for the B. anthracis enzyme and compared with those of three bacterial IMPDHs from Campylobacter jejuni, Clostridium perfringens, and Vibrio cholerae. The structures contribute to the characterization of the active site and design of inhibitors that specifically target B. anthracis and other microbial IMPDH enzymes.

Bacillus anthracis inosine 5'-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes.,Makowska-Grzyska M, Kim Y, Wu R, Wilton R, Gollapalli DR, Wang XK, Zhang R, Jedrzejczak R, Mack JC, Maltseva N, Mulligan R, Binkowski TA, Gornicki P, Kuhn ML, Anderson WF, Hedstrom L, Joachimiak A Biochemistry. 2012 Aug 7;51(31):6148-63. Epub 2012 Jul 25. PMID:22788966<ref>PMID:22788966</ref>

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

==See Also==
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus anthracis str. Ames]]
[[Category: Large Structures]]
[[Category: Anderson WF]]
[[Category: CSGID]]
[[Category: Gu M]]
[[Category: Joachimiak A]]
[[Category: Kim Y]]
[[Category: Wu R]]
[[Category: Zhang R]]