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4aic

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Revision as of 05:35, 25 August 2022

X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with fosmidomycin, manganese and NADPH

Structural highlights

4aic is a 2 chain structure with sequence from Myctu. This structure supersedes the now removed PDB entry 2jcz. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	2c82, 2jcv, 2jcx, 2jcy, 2jd0, 2jd1, 2jd2, 2y1c, 2y1d, 2y1e, 2y1f, 2y1g, 4a03
Activity:	1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Isopentenyl diphosphate is the precursor of various isoprenoids that are essential to all living organisms. It is produced by the mevalonate pathway in humans but by an alternate route in plants, protozoa, and many bacteria. 1-deoxy-D-xylulose-5-phosphate reductoisomerase catalyzes the second step of this non-mevalonate pathway, which involves an NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose 5-phosphate to form 2-C-methyl-D-erythritol 4-phosphate. The use of different pathways, combined with the reported essentiality of the enzyme makes the reductoisomerase a highly promising target for drug design. Here we present several high resolution structures of the Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase, representing both wild type and mutant enzyme in various complexes with Mn(2+), NADPH, and the known inhibitor fosmidomycin. The asymmetric unit corresponds to the biological homodimer. Although crystal contacts stabilize an open active site in the B molecule, the A molecule displays a closed conformation, with some differences depending on the ligands bound. An inhibition study with fosmidomycin resulted in an estimated IC(50) value of 80 nm. The double mutant enzyme (D151N/E222Q) has lost its ability to bind the metal and, thereby, also its activity. Our structural information complemented with molecular dynamics simulations and free energy calculations provides the framework for the design of new inhibitors and gives new insights into the reaction mechanism. The conformation of fosmidomycin bound to the metal ion is different from that reported in a previously published structure and indicates that a rearrangement of the intermediate is not required during catalysis.

Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis.,Henriksson LM, Unge T, Carlsson J, Aqvist J, Mowbray SL, Jones TA J Biol Chem. 2007 Jul 6;282(27):19905-16. Epub 2007 May 9. PMID:17491006^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Henriksson LM, Unge T, Carlsson J, Aqvist J, Mowbray SL, Jones TA. Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis. J Biol Chem. 2007 Jul 6;282(27):19905-16. Epub 2007 May 9. PMID:17491006 doi:10.1074/jbc.M701935200

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4aic"

@@ Line 3: / Line 3: @@
 <StructureSection load='4aic' size='340' side='right'caption='[[4aic]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4aic]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2jcz 2jcz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AIC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AIC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4aic]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2jcz 2jcz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AIC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FOM:3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>FOM</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FOM:3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>FOM</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c82|2c82]], [[2jcv|2jcv]], [[2jcx|2jcx]], [[2jcy|2jcy]], [[2jd0|2jd0]], [[2jd1|2jd1]], [[2jd2|2jd2]], [[2y1c|2y1c]], [[2y1d|2y1d]], [[2y1e|2y1e]], [[2y1f|2y1f]], [[2y1g|2y1g]], [[4a03|4a03]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2c82|2c82]], [[2jcv|2jcv]], [[2jcx|2jcx]], [[2jcy|2jcy]], [[2jd0|2jd0]], [[2jd1|2jd1]], [[2jd2|2jd2]], [[2y1c|2y1c]], [[2y1d|2y1d]], [[2y1e|2y1e]], [[2y1f|2y1f]], [[2y1g|2y1g]], [[4a03|4a03]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [https://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=4aic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aic OCA], [http://pdbe.org/4aic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4aic RCSB], [http://www.ebi.ac.uk/pdbsum/4aic PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4aic 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=4aic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aic OCA], [https://pdbe.org/4aic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aic RCSB], [https://www.ebi.ac.uk/pdbsum/4aic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aic ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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).
+[[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;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 ==See Also==
 *[[DXP reductoisomerase|DXP reductoisomerase]]
-*[[User:Wayne Decatur/UNH BCHEM833 Structural Analysis Workshop Session Fall 2012|User:Wayne Decatur/UNH BCHEM833 Structural Analysis Workshop Session Fall 2012]]
 == References ==
 <references/>
@@ Line 29: / Line 28: @@
 </StructureSection>
 [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]]
+[[Category: Large Structures]]
 [[Category: Myctu]]
 [[Category: Henriksson, L M]]

4aic

From Proteopedia

Revision as of 05:35, 25 August 2022

X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with fosmidomycin, manganese and NADPH

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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