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| | ==Crystal structure of the mutant T159S of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP== | | ==Crystal structure of the mutant T159S of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP== |
| - | <StructureSection load='3p5z' size='340' side='right' caption='[[3p5z]], [[Resolution|resolution]] 1.30Å' scene=''> | + | <StructureSection load='3p5z' size='340' side='right'caption='[[3p5z]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p5z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Metth Metth]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P5Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p5z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus_str._Delta_H Methanothermobacter thermautotrophicus str. Delta H]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P5Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><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>, <scene name='pdbligand=POL:N-PROPANOL'>POL</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]] 1.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ltp|3ltp]], [[3p5y|3p5y]], [[3p60|3p60]], [[3p61|3p61]]</td></tr>
| + | <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>, <scene name='pdbligand=POL:N-PROPANOL'>POL</scene></td></tr> |
| - | <tr id='gene'><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=187420 METTH])</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=3p5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5z OCA], [https://pdbe.org/3p5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p5z RCSB], [https://www.ebi.ac.uk/pdbsum/3p5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5z 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/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> | + | |
| - | <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=3p5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5z OCA], [http://pdbe.org/3p5z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p5z RCSB], [http://www.ebi.ac.uk/pdbsum/3p5z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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] | + | [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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3p5z" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3p5z" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Metth]] | + | [[Category: Large Structures]] |
| - | [[Category: Orotidine-5'-phosphate decarboxylase]] | + | [[Category: Methanothermobacter thermautotrophicus str. Delta H]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Fedorov, A A]] | + | [[Category: Fedorov AA]] |
| - | [[Category: Fedorov, E V]] | + | [[Category: Fedorov EV]] |
| - | [[Category: Gerlt, J A]] | + | [[Category: Gerlt JA]] |
| - | [[Category: Wood, B M]] | + | [[Category: Wood BM]] |
| - | [[Category: Inhibitor bmp]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Orotidine 5'-monophosphate decarboxylase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
Function
PYRF_METTH Catalyzes the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP).[HAMAP-Rule:MF_01200_A]
Publication Abstract from PubMed
The binding of a ligand to orotidine 5'-monophosphate decarboxylase (OMPDC) is accompanied by a conformational change from an open, inactive conformation (E(o)) to a closed, active conformation (E(c)). As the substrate traverses the reaction coordinate to form the stabilized vinyl carbanion/carbene intermediate, interactions that destabilize the carboxylate group of the substrate and stabilize the intermediate (in the E(c).S() complex) are enforced. Focusing on the OMPDC from Methanothermobacter thermautotrophicus, we find the "remote" 5'-phosphate group of the substrate activates the enzyme 2.4 x 10(8)-fold; the activation is equivalently described by an intrinsic binding energy (IBE) of 11.4 kcal/mol. We studied residues in the activation that (1) directly contact the 5'-phosphate group, (2) participate in a hydrophobic cluster near the base of the active site loop that sequesters the bound substrate from the solvent, and (3) form hydrogen bonding interactions across the interface between the "mobile" and "fixed" half-barrel domains of the (beta/alpha)(8)-barrel structure. Our data support a model in which the IBE provided by the 5'-phosphate group is used to allow interactions both near the N-terminus of the active site loop and across the domain interface that stabilize both the E(c).S and E(c).S() complexes relative to the E(o).S complex. The conclusion that the IBE of the 5'-phosphate group provides stabilization to both the E(c).S and E(c).S() complexes, not just the E(c).S() complex, is central to understanding the structural origins of enzymatic catalysis as well as the requirements for the de novo design of enzymes that catalyze novel reactions.
Conformational Changes in Orotidine 5'-Monophosphate Decarboxylase: A Structure-Based Explanation for How the 5'-Phosphate Group Activates the Enzyme.,Desai BJ, Wood BM, Fedorov AA, Fedorov EV, Goryanova B, Amyes TL, Richard JP, Almo SC, Gerlt JA Biochemistry. 2012 Oct 17. PMID:23030629[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Desai BJ, Wood BM, Fedorov AA, Fedorov EV, Goryanova B, Amyes TL, Richard JP, Almo SC, Gerlt JA. Conformational Changes in Orotidine 5'-Monophosphate Decarboxylase: A Structure-Based Explanation for How the 5'-Phosphate Group Activates the Enzyme. Biochemistry. 2012 Oct 17. PMID:23030629 doi:10.1021/bi301188k
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