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1sjn

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Mycobacterium tuberculosis dUTPase complexed with magnesium and alpha,beta-imido-dUTP

Structural highlights

1sjn is a 3 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DUT_MYCTU This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[HAMAP-Rule:MF_00116]

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 structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution in complex with magnesium ion and the non-hydrolyzable substrate analog, alpha,beta-imido dUTP. dUTPase is an enzyme essential for depleting potentially toxic concentrations of dUTP in the cell. Given the importance of its biological role, it has been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosis infection in humans. The crystal structure presented here offers some insight into the potential for designing a specific inhibitor of the M.tuberculosis dUTPase enzyme. The structure also offers new insights into the mechanism of dUTP hydrolysis by providing an accurate representation of the enzyme-substrate complex in which both the metal ion and dUTP analog are included. The structure suggests that inclusion of a magnesium ion is important for stabilizing the position of the alpha-phosphorus for an in-line nucleophilic attack. In the absence of magnesium, the alpha-phosphate of dUTP can have either of the two positions which differ by 4.5 Angstrom. A transiently ordered C-terminal loop further assists catalysis by shielding the general base, Asp83, from solvent thus elevating its pK(a) so that it might in turn activate a tightly bound water molecule for nucleophilic attack. The metal ion coordinates alpha, beta, and gamma phosphate groups with tridentate geometry identical with that observed in the crystal structure of DNA polymerase beta complexed with magnesium and dNTP analog, revealing some common features in catalytic mechanism.

Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism.,Chan S, Segelke B, Lekin T, Krupka H, Cho US, Kim MY, So M, Kim CY, Naranjo CM, Rogers YC, Park MS, Waldo GS, Pashkov I, Cascio D, Perry JL, Sawaya MR J Mol Biol. 2004 Aug 6;341(2):503-17. PMID:15276840^[1]

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

References

↑ Chan S, Segelke B, Lekin T, Krupka H, Cho US, Kim MY, So M, Kim CY, Naranjo CM, Rogers YC, Park MS, Waldo GS, Pashkov I, Cascio D, Perry JL, Sawaya MR. Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism. J Mol Biol. 2004 Aug 6;341(2):503-17. PMID:15276840 doi:http://dx.doi.org/10.1016/j.jmb.2004.06.028

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sjn"

@@ Line 3: / Line 3: @@
 <StructureSection load='1sjn' size='340' side='right'caption='[[1sjn]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1sjn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1SJN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1sjn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SJN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1six|1six]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUT, RV2697C, MT2771, MTCY05A6.18C, MB2716C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=1sjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sjn OCA], [https://pdbe.org/1sjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sjn RCSB], [https://www.ebi.ac.uk/pdbsum/1sjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sjn 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/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1sjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sjn OCA], [http://pdbe.org/1sjn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1sjn RCSB], [http://www.ebi.ac.uk/pdbsum/1sjn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1sjn ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DUT_MYCTU DUT_MYCTU]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[HAMAP-Rule:MF_00116]
+[https://www.uniprot.org/uniprot/DUT_MYCTU DUT_MYCTU] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[HAMAP-Rule:MF_00116]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: DUTP diphosphatase]]
+[[Category: Mycobacterium tuberculosis]]
-[[Category: Cascio, D]]
+[[Category: Cascio D]]
-[[Category: Chan, S]]
+[[Category: Chan S]]
-[[Category: Cho, U S]]
+[[Category: Cho US]]
-[[Category: Eisenberg, D]]
+[[Category: Eisenberg D]]
-[[Category: Kim, C Y]]
+[[Category: Kim C-Y]]
-[[Category: Kim, M Y]]
+[[Category: Kim M-Y]]
-[[Category: Krupka, H]]
+[[Category: Krupka H]]
-[[Category: Lekin, T]]
+[[Category: Lekin T]]
-[[Category: Naranjo, C M]]
+[[Category: Naranjo CM]]
-[[Category: Park, M S]]
+[[Category: Park MS]]
-[[Category: Pashkov, I]]
+[[Category: Pashkov I]]
-[[Category: Perry, J L]]
+[[Category: Perry JL]]
-[[Category: Rogers, Y C]]
+[[Category: Rogers YC]]
-[[Category: Sawaya, M R]]
+[[Category: Sawaya MR]]
-[[Category: Segelke, B]]
+[[Category: Segelke B]]
-[[Category: So, M]]
+[[Category: So M]]
-[[Category: Structural genomic]]
+[[Category: Terwilliger TC]]
-[[Category: Terwilliger, T C]]
+[[Category: Waldo GS]]
-[[Category: Waldo, G S]]
+[[Category: Yeates TO]]
-[[Category: Yeates, T O]]
-[[Category: Hydrolase]]
-[[Category: Jelly-roll]]
-[[Category: PSI, Protein structure initiative]]
-[[Category: Tbsgc]]

1sjn

From Proteopedia

Current revision

Mycobacterium tuberculosis dUTPase complexed with magnesium and alpha,beta-imido-dUTP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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