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| | <StructureSection load='4rcv' size='340' side='right'caption='[[4rcv]], [[Resolution|resolution]] 2.29Å' scene=''> | | <StructureSection load='4rcv' size='340' side='right'caption='[[4rcv]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rcv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RCV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rcv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RCV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DE2:1-DEOXY-L-ERYTHRULOSE'>DE2</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DE2:1-DEOXY-L-ERYTHRULOSE'>DE2</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ooe|4ooe]], [[4oof|4oof]]</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=4rcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcv OCA], [https://pdbe.org/4rcv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rcv RCSB], [https://www.ebi.ac.uk/pdbsum/4rcv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcv ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dxr, P425_02990, RVBD_2870c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267 1.1.1.267] </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=4rcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcv OCA], [http://pdbe.org/4rcv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rcv RCSB], [http://www.ebi.ac.uk/pdbsum/4rcv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/I6YAH0_MYCTU I6YAH0_MYCTU]] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity).[HAMAP-Rule:MF_00183][SAAS:SAAS026877_004_013509] | + | [https://www.uniprot.org/uniprot/DXR_MYCTU DXR_MYCTU] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[DXP reductoisomerase|DXP reductoisomerase]] | + | *[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Allen, C L]] | + | [[Category: Allen CL]] |
| - | [[Category: Gulick, A M]] | + | [[Category: Gulick AM]] |
| - | [[Category: Kholodar, S A]] | + | [[Category: Kholodar SA]] |
| - | [[Category: Murkin, A S]] | + | [[Category: Murkin AS]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductoisomerase]]
| + | |
| Structural highlights
Function
DXR_MYCTU Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity).
Publication Abstract from PubMed
Several mechanistically unrelated enzymes utilize the binding energy of their substrate's nonreacting phosphoryl group to accelerate catalysis. Evidence for the involvement of the phosphodianion in transition state formation has come from reactions of the substrate in pieces, in which reaction of a truncated substrate lacking its phosphorylmethyl group is activated by inorganic phosphite. What has remained unknown until now is how the phosphodianion group influences the reaction energetics at different points along the reaction coordinate. 1-Deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase (DXR), which catalyzes the isomerization of DXP to 2-C-methyl-d-erythrose 4-phosphate (MEsP) and subsequent NADPH-dependent reduction, presents a unique opportunity to address this concern. Previously, we have reported the effect of covalently linked phosphate on the energetics of DXP turnover. Through the use of chemically synthesized MEsP and its phosphate-truncated analogue, 2-C-methyl-d-glyceraldehyde, the current study revealed a loss of 6.1 kcal/mol of kinetic barrier stabilization upon truncation, of which 4.4 kcal/mol was regained in the presence of phosphite dianion. The activating effect of phosphite was accompanied by apparent tightening of its interactions within the active site at the intermediate stage of the reaction, suggesting a role of the phosphodianion in disfavoring intermediate release and in modulation of the on-enzyme isomerization equilibrium. The results of kinetic isotope effect and structural studies indicate rate limitation by physical steps when the covalent linkage is severed. These striking differences in the energetics of the natural reaction and the reactions in pieces provide a deeper insight into the contribution of enzyme-phosphodianion interactions to the reaction coordinate.
The role of phosphate in a multistep enzymatic reaction: reactions of the substrate and intermediate in pieces.,Kholodar SA, Allen CL, Gulick AM, Murkin AS J Am Chem Soc. 2015 Feb 25;137(7):2748-56. doi: 10.1021/ja512911f. Epub 2015 Feb , 10. PMID:25642788[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kholodar SA, Allen CL, Gulick AM, Murkin AS. The role of phosphate in a multistep enzymatic reaction: reactions of the substrate and intermediate in pieces. J Am Chem Soc. 2015 Feb 25;137(7):2748-56. doi: 10.1021/ja512911f. Epub 2015 Feb , 10. PMID:25642788 doi:http://dx.doi.org/10.1021/ja512911f
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