5edd: Difference between revisions
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==Crystal structure of Mycobacterium tuberculosis dUTPase R140K, H145W mutant== | |||
<StructureSection load='5edd' size='340' side='right' caption='[[5edd]], [[Resolution|resolution]] 1.97Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5edd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EDD FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gcy|4gcy]], [[3loj|3loj]], [[3h6d|3h6d]], [[3hza|3hza]], [[3i93|3i93]], [[2py4|2py4]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5edd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5edd OCA], [http://pdbe.org/5edd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5edd RCSB], [http://www.ebi.ac.uk/pdbsum/5edd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5edd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/DUT_MYCTA DUT_MYCTA]] 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the gamma-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all the above properties, all essential arginine fingers are used to catalyze the cleavage of the gamma-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its direct nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the gamma-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained based on the unique chemistry performed by the pyrophosphatase dUTPases. | |||
Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases.,Nagy GN, Suardiaz R, Lopata A, Ozohanics O, Vekey K, Brooks BR, Leveles I, Toth J, Vertessy BG, Rosta E J Am Chem Soc. 2016 Oct 14. PMID:27740761<ref>PMID:27740761</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 5edd" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: DUTP diphosphatase]] | |||
[[Category: Harmat, V]] | [[Category: Harmat, V]] | ||
[[Category: Leveles, I]] | [[Category: Leveles, I]] | ||
[[Category: Lopata, A]] | [[Category: Lopata, A]] | ||
[[Category: Nagy, G | [[Category: Nagy, G N]] | ||
[[Category: Vertessy, G | [[Category: Toth, J]] | ||
[[Category: Vertessy, G B]] | |||
[[Category: Enzyme-ligand complex]] | |||
[[Category: Hydrolase]] | |||
[[Category: Jelly-roll]] | |||
Revision as of 21:20, 2 November 2016
Crystal structure of Mycobacterium tuberculosis dUTPase R140K, H145W mutantCrystal structure of Mycobacterium tuberculosis dUTPase R140K, H145W mutant
Structural highlights
Function[DUT_MYCTA] 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. Publication Abstract from PubMedArginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the gamma-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all the above properties, all essential arginine fingers are used to catalyze the cleavage of the gamma-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its direct nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the gamma-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained based on the unique chemistry performed by the pyrophosphatase dUTPases. Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases.,Nagy GN, Suardiaz R, Lopata A, Ozohanics O, Vekey K, Brooks BR, Leveles I, Toth J, Vertessy BG, Rosta E J Am Chem Soc. 2016 Oct 14. PMID:27740761[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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