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| | ==Crystal Structure of a Novel Diadenosine 5',5'''-P1,P4-Tetraphosphate Phosphorylase from Mycobacterium tuberculosis H37Rv== | | ==Crystal Structure of a Novel Diadenosine 5',5'''-P1,P4-Tetraphosphate Phosphorylase from Mycobacterium tuberculosis H37Rv== |
| - | <StructureSection load='3ano' size='340' side='right' caption='[[3ano]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='3ano' size='340' side='right'caption='[[3ano]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ano]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_sp._h37rv Mycobacterium sp. h37rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ANO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ANO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ano]] 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=3ANO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ANO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.894Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT2688, Rv2613c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 Mycobacterium sp. H37Rv])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ATP_adenylyltransferase ATP adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.53 2.7.7.53] </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=3ano FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ano OCA], [https://pdbe.org/3ano PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ano RCSB], [https://www.ebi.ac.uk/pdbsum/3ano PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ano ProSAT]</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=3ano FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ano OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ano RCSB], [http://www.ebi.ac.uk/pdbsum/3ano PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AP4A_MYCTU AP4A_MYCTU]] Catabolizes diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) into ADP and ATP. It does not catalyze the reverse phosphorolysis reaction. The optimum substrates are dinucleoside polyphosphates containing four or five phosphate residues.<ref>PMID:19778616</ref> <ref>PMID:21565198</ref> | + | [https://www.uniprot.org/uniprot/AP4A_MYCTU AP4A_MYCTU] Catabolizes diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) into ADP and ATP. It does not catalyze the reverse phosphorolysis reaction. The optimum substrates are dinucleoside polyphosphates containing four or five phosphate residues.<ref>PMID:19778616</ref> <ref>PMID:21565198</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Rv2613c is a diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) phosphorylase from Mycobacterium tuberculosis H37Rv. Sequence analysis suggests that Rv2613c belongs to the histidine triad (HIT) motif superfamily, which includes HIT family diadenosine polyphosphate (Ap(n)A) hydrolases and Ap(4)A phosphorylases. However, the amino acid sequence of Rv2613c is more similar to that of HIT family Ap(n)A hydrolases than to that of typical Ap(4)A phosphorylases. Here, we report the crystal structure of Rv2613c, which is the first structure of a protein with Ap(n)A phosphorylase activity, and characterized the structural basis of its catalytic activity. Our results showed that the structure of Rv2613c is similar to those of other HIT superfamily proteins. However, Asn139, Gly146, and Ser147 in the active site of Rv2613c replace the corresponding Gln, Gln, and Thr residues that are normally found in HIT family Ap(n)A hydrolases. Furthermore, analyses of Rv2613c mutants revealed that Asn139, Gly146, and Ser147 are important active-site residues and that Asn139 has a critical role in catalysis. The position of Gly146 might influence the phosphorylase activity. In addition, the tetrameric structure of Rv2613c and the presence of Trp160 might be essential for the formation of the Ap(4)A binding site. These structural insights into Rv2613c may facilitate the development of novel structure-based inhibitors for treating tuberculosis.
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| - | Structural insights into the novel diadenosine 5',5'''-P(1),P(4)-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.,Mori S, Shibayama K, Wachino J, Arakawa Y J Mol Biol. 2011 Jul 1;410(1):93-104. doi: 10.1016/j.jmb.2011.04.059. Epub 2011, May 4. PMID:21565198<ref>PMID:21565198</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: ATP adenylyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Mycobacterium sp. h37rv]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Arakawa, Y]] | + | [[Category: Arakawa Y]] |
| - | [[Category: Mori, S]] | + | [[Category: Mori S]] |
| - | [[Category: Shibayama, K]] | + | [[Category: Shibayama K]] |
| - | [[Category: Wachino, J]] | + | [[Category: Wachino J]] |
| - | [[Category: Diadenosine polyphosphate]]
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| - | [[Category: Hit motif]]
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| - | [[Category: Mycobacterium]]
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| - | [[Category: Phosphorylase]]
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| - | [[Category: Transferase]]
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