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3nqm

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==Crystal structure of the mutant V155S of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP==
==Crystal structure of the mutant V155S of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP==
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<StructureSection load='3nqm' size='340' side='right' caption='[[3nqm]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
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<StructureSection load='3nqm' size='340' side='right'caption='[[3nqm]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3nqm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NQM FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3nqm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NQM FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMP:6-HYDROXYURIDINE-5-PHOSPHATE'>BMP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.32&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3g18|3g18]], [[3nq6|3nq6]], [[3nq7|3nq7]], [[3nqa|3nqa]], [[3nqc|3nqc]], [[3nqd|3nqd]], [[3nqe|3nqe]], [[3nqf|3nqf]], [[3nqg|3nqg]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMP:6-HYDROXYURIDINE-5-PHOSPHATE'>BMP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pyrF, MTH_129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=145262 Methanothermobacter thermautotrophicus])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nqm OCA], [https://pdbe.org/3nqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nqm RCSB], [https://www.ebi.ac.uk/pdbsum/3nqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nqm ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] </span></td></tr>
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</table>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nqm RCSB], [http://www.ebi.ac.uk/pdbsum/3nqm PDBsum]</span></td></tr>
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== Function ==
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<table>
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[https://www.uniprot.org/uniprot/PYRF_METTH PYRF_METTH] Catalyzes the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP).[HAMAP-Rule:MF_01200_A]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) is accompanied by exceptional values for rate enhancement (k(cat)/k(non) = 7.1 x 10(16)) and catalytic proficiency [(k(cat)/K(M))/k(non) = 4.8 x 10(22) M(-1)]. Although a stabilized vinyl carbanion/carbene intermediate is located on the reaction coordinate, the structural strategies by which the reduction in the activation energy barrier is realized remain incompletely understood. This laboratory recently reported that "substrate destabilization" by Asp 70 in the OMPDC from Methanothermobacter thermoautotrophicus (MtOMPDC) lowers the activation energy barrier by approximately 5 kcal/mol (contributing approximately 2.7 x 10(3) to the rate enhancement) [Chan, K. K., Wood, B. M., Fedorov, A. A., Fedorov, E. V., Imker, H. J., Amyes, T. L., Richard, J. P., Almo, S. C., and Gerlt, J. A. (2009) Biochemistry 48, 5518-5531]. We now report that substitutions of hydrophobic residues in a pocket proximal to the carboxylate group of the substrate (Ile 96, Leu 123, and Val 155) with neutral hydrophilic residues decrease the value of k(cat) by as much as 400-fold but have a minimal effect on the value of k(ex) for exchange of H6 of the FUMP product analogue with solvent deuterium; we hypothesize that this pocket destabilizes the substrate by preventing hydration of the substrate carboxylate group. We also report that substitutions of Ser 127 that is proximal to O4 of the orotate ring decrease the value of k(cat)/K(M), with the S127P substitution that eliminates hydrogen bonding interactions with O4 producing a 2.5 x 10(6)-fold reduction; this effect is consistent with delocalization of the negative charge of the carbanionic intermediate on O4 that produces an anionic carbene intermediate and thereby provides a structural strategy for stabilization of the intermediate. These observations provide additional information about the identities of the active site residues that contribute to the rate enhancement and, therefore, insights into the structural strategies for catalysis.
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Mechanism of the Orotidine 5'-Monophosphate Decarboxylase-Catalyzed Reaction: Importance of Residues in the Orotate Binding Site.,Iiams V, Desai BJ, Fedorov AA, Fedorov EV, Almo SC, Gerlt JA Biochemistry. 2011 Sep 6. PMID:21870810<ref>PMID:21870810</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Large Structures]]
[[Category: Methanothermobacter thermautotrophicus]]
[[Category: Methanothermobacter thermautotrophicus]]
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[[Category: Orotidine-5'-phosphate decarboxylase]]
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[[Category: Almo SC]]
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[[Category: Almo, S C.]]
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[[Category: Fedorov AA]]
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[[Category: Fedorov, A A.]]
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[[Category: Fedorov EV]]
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[[Category: Fedorov, E V.]]
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[[Category: Gerlt JA]]
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[[Category: Gerlt, J A.]]
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[[Category: Wood BM]]
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[[Category: Wood, B M.]]
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[[Category: Bmp]]
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[[Category: Lyase-lyase inhibitor complex]]
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[[Category: Methanobacterium thermoautotrophicum]]
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[[Category: Orotidine 5'-monophosphate decarboxylase]]
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Current revision

Crystal structure of the mutant V155S of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP

PDB ID 3nqm

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