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| | <StructureSection load='5k1z' size='340' side='right'caption='[[5k1z]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='5k1z' size='340' side='right'caption='[[5k1z]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k1z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_43504 Atcc 43504]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K1Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5K1Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k1z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K1Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CT:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-{[(4-CHLOROPHENYL)SULFANYL]METHYL}PYRROLIDIN-3-OL'>4CT</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jpc|5jpc]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CT:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-{[(4-CHLOROPHENYL)SULFANYL]METHYL}PYRROLIDIN-3-OL'>4CT</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene></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=210 ATCC 43504])</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=5k1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k1z OCA], [https://pdbe.org/5k1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k1z RCSB], [https://www.ebi.ac.uk/pdbsum/5k1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k1z ProSAT]</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=5k1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k1z OCA], [http://pdbe.org/5k1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k1z RCSB], [http://www.ebi.ac.uk/pdbsum/5k1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k1z 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 43504]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Banco, M T]] | |
| - | [[Category: Kovalevsky, A Y]] | |
| - | [[Category: Ronning, D R]] | |
| | [[Category: Helicobacter pylori]] | | [[Category: Helicobacter pylori]] |
| - | [[Category: Hydrolase]] | + | [[Category: Large Structures]] |
| - | [[Category: Joint neutron and x-ray]] | + | [[Category: Banco MT]] |
| - | [[Category: Neutron]] | + | [[Category: Kovalevsky AY]] |
| - | [[Category: Nucleosidase]] | + | [[Category: Ronning DR]] |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ronning DR, Iacopelli NM, Mishra V. Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Protein Sci. 2010 Oct 15. PMID:20954236 doi:10.1002/pro.524
- ↑ Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL. A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori. Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633 doi:http://dx.doi.org/10.1021/bi3009664
- ↑ Banco MT, Mishra V, Ostermann A, Schrader TE, Evans GB, Kovalevsky A, Ronning DR. Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13756-13761. Epub 2016 Nov 16. PMID:27856757 doi:http://dx.doi.org/10.1073/pnas.1609718113
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