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| | <StructureSection load='5ccd' size='340' side='right'caption='[[5ccd]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='5ccd' size='340' side='right'caption='[[5ccd]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ccd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Campylobacter_pylori_j99 Campylobacter pylori j99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CCD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CCD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ccd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_J99 Helicobacter pylori J99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CCD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CCD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Hybrid , Neutron Diffraction , X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mtnN, mtn, jhp_0082 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=85963 Campylobacter pylori J99])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></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=5ccd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ccd OCA], [http://pdbe.org/5ccd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ccd RCSB], [http://www.ebi.ac.uk/pdbsum/5ccd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ccd 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=5ccd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ccd OCA], [https://pdbe.org/5ccd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ccd RCSB], [https://www.ebi.ac.uk/pdbsum/5ccd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ccd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MQMTN_HELPJ MQMTN_HELPJ]] Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Can also probably use S-adenosylhomocysteine (SAH) as substrate, leading to adenine and S-ribosylhomocysteine. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2.<ref>PMID:20954236</ref> <ref>PMID:22891633</ref> | + | [https://www.uniprot.org/uniprot/MQMTN_HELPJ MQMTN_HELPJ] Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Can also probably use S-adenosylhomocysteine (SAH) as substrate, leading to adenine and S-ribosylhomocysteine. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2.<ref>PMID:20954236</ref> <ref>PMID:22891633</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | MTAN (5'-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pKa above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH), Formycin A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyr rolidine (p-ClPh-Thio-DADMe-ImmA) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-ImmA and ImmA analogs.
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| - | Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states.,Banco MT, Mishra V, Ostermann A, Schrader TE, Evans GB, Kovalevsky A, Ronning DR Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13756-13761. Epub 2016 Nov 16. PMID:27856757<ref>PMID:27856757</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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| - | <div class="pdbe-citations 5ccd" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Campylobacter pylori j99]] | + | [[Category: Helicobacter pylori J99]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Banco, M T]] | + | [[Category: Banco MT]] |
| - | [[Category: Kovalevsky, A Y]] | + | [[Category: Kovalevsky AY]] |
| - | [[Category: Ronning, D R]] | + | [[Category: Ronning DR]] |
| - | [[Category: Helicobacter pylori]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: N-glycosyl hydrolase]]
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| - | [[Category: Neutron]]
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| - | [[Category: S-adenosylhomocysteine]]
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