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| | <StructureSection load='3li0' size='340' side='right'caption='[[3li0]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='3li0' size='340' side='right'caption='[[3li0]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3li0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Metth Metth]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LI0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3li0]] 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=3LI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LI0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMQ:1-(5-PHOSPHO-BETA-D-RIBOFURANOSYL)BARBITURIC+ACID'>BMQ</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]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3lht|3lht]], [[3lhu|3lhu]], [[3lhv|3lhv]], [[3lhw|3lhw]], [[3lhy|3lhy]], [[3lhz|3lhz]], [[3li1|3li1]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMQ:1-(5-PHOSPHO-BETA-D-RIBOFURANOSYL)BARBITURIC+ACID'>BMQ</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pyrF, MTH_129 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=187420 METTH])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3li0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3li0 OCA], [https://pdbe.org/3li0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3li0 RCSB], [https://www.ebi.ac.uk/pdbsum/3li0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3li0 ProSAT]</span></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=3li0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3li0 OCA], [https://pdbe.org/3li0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3li0 RCSB], [https://www.ebi.ac.uk/pdbsum/3li0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3li0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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]
| + | [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] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Metth]] | + | [[Category: Methanothermobacter thermautotrophicus str. Delta H]] |
| - | [[Category: Orotidine-5'-phosphate decarboxylase]]
| + | [[Category: Almo SC]] |
| - | [[Category: Almo, S C]] | + | [[Category: Fedorov AA]] |
| - | [[Category: Fedorov, A A]] | + | [[Category: Fedorov EV]] |
| - | [[Category: Fedorov, E V]] | + | [[Category: Gerlt JA]] |
| - | [[Category: Gerlt, J A]] | + | [[Category: Wood BM]] |
| - | [[Category: Wood, B M]] | + | |
| - | [[Category: 6-hydroxyuridine-5'-phosphate]]
| + | |
| - | [[Category: Decarboxylase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Mutant r203a]]
| + | |
| - | [[Category: Pyrimidine biosynthesis]]
| + | |
| Structural highlights
Function
PYRF_METTH Catalyzes the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP).[HAMAP-Rule:MF_01200_A]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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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