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| | ==Crystal Structure of Inosine-5'-monophosphate Dehydrogenase from Bacillus anthracis str. Ames complexed with XMP== | | ==Crystal Structure of Inosine-5'-monophosphate Dehydrogenase from Bacillus anthracis str. Ames complexed with XMP== |
| - | <StructureSection load='3tsd' size='340' side='right' caption='[[3tsd]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='3tsd' size='340' side='right'caption='[[3tsd]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tsd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_(strain_ames) Bacillus anthracis (strain ames)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TSD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tsd]] 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=3TSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TSD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5-MONOPHOSPHATE'>XMP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.653Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tsb|3tsb]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5-MONOPHOSPHATE'>XMP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">guaB, BAS0011, BA_0008, GBAA_0008 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=198094 Bacillus anthracis (strain Ames)])</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=3tsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tsd OCA], [https://pdbe.org/3tsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tsd RCSB], [https://www.ebi.ac.uk/pdbsum/3tsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tsd ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tsd OCA], [http://pdbe.org/3tsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tsd RCSB], [http://www.ebi.ac.uk/pdbsum/3tsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tsd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q81W29_BACAN Q81W29_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 (By similarity).[HAMAP-Rule:MF_01964] | + | [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] |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | 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.
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| - | 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>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3tsd" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Inosine monophosphate dehydrogenase|Inosine monophosphate dehydrogenase]] | + | *[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: IMP dehydrogenase]] | + | [[Category: Bacillus anthracis str. Ames]] |
| - | [[Category: Anderson, W F]] | + | [[Category: Large Structures]] |
| - | [[Category: Hasseman, J]] | + | [[Category: Anderson WF]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Hasseman J]] |
| - | [[Category: Kim, Y]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Makowska-Grzyska, M]] | + | [[Category: Kim Y]] |
| - | [[Category: Cbs domain]]
| + | [[Category: Makowska-Grzyska M]] |
| - | [[Category: Structural genomic]]
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| - | [[Category: Csgid]]
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| - | [[Category: Cytosol]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Tim barrel]]
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