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| | ==Crystal structure of Campylobacter jejuni 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with 5'-deoxy-5'-Propyl-DADMe-Immucillin-A== | | ==Crystal structure of Campylobacter jejuni 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with 5'-deoxy-5'-Propyl-DADMe-Immucillin-A== |
| - | <StructureSection load='6ayo' size='340' side='right' caption='[[6ayo]], [[Resolution|resolution]] 1.67Å' scene=''> | + | <StructureSection load='6ayo' size='340' side='right'caption='[[6ayo]], [[Resolution|resolution]] 1.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ayo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"campylobacter_fetus_subsp._jejuni"_smibert_1974 "campylobacter fetus subsp. jejuni" smibert 1974]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ayo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Campylobacter_jejuni Campylobacter jejuni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AYO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=C1Y:(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-propylpyrrolidin-3-ol'>C1Y</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.67Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">A0M70_07260, AJY53_05400 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=197 "Campylobacter fetus subsp. jejuni" Smibert 1974])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=C1Y:(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-propylpyrrolidin-3-ol'>C1Y</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteine_nucleosidase Adenosylhomocysteine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.9 3.2.2.9] </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=6ayo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayo OCA], [https://pdbe.org/6ayo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ayo RCSB], [https://www.ebi.ac.uk/pdbsum/6ayo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayo 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=6ayo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayo OCA], [http://pdbe.org/6ayo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayo RCSB], [http://www.ebi.ac.uk/pdbsum/6ayo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A1E7P7U4_CAMJU A0A1E7P7U4_CAMJU]] Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH/AdoHcy) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively.[SAAS:SAAS00679308] | + | [https://www.uniprot.org/uniprot/MQMTN_CAMJE MQMTN_CAMJE] 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 Campylobacter 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. Shows negligible activity with futalosine (FL) as substrate.<ref>PMID:21489995</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: Campylobacter fetus subsp. jejuni smibert 1974]] | + | [[Category: Campylobacter jejuni]] |
| - | [[Category: Adenosylhomocysteine nucleosidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Bonanno, J B]] | + | [[Category: Bonanno JB]] |
| - | [[Category: Ducati, R G]] | + | [[Category: Ducati RG]] |
| - | [[Category: Harijan, R K]] | + | [[Category: Harijan RK]] |
| - | [[Category: Schramm, V L]] | + | [[Category: Schramm VL]] |
| - | [[Category: Foodborne disease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mtan enzyme]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
MQMTN_CAMJE 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 Campylobacter 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. Shows negligible activity with futalosine (FL) as substrate.[1]
Publication Abstract from PubMed
Campylobacter jejuni is a Gram-negative bacterium responsible for food-borne gastroenteritis and associated with Guillain-Barre, Reiter, and irritable bowel syndromes. Antibiotic resistance in C. jejuni is common, creating a need for antibiotics with novel mechanisms of action. Menaquinone biosynthesis in C. jejuni uses the rare futalosine pathway, where 5'-methylthioadenosine nucleosidase ( CjMTAN) is proposed to catalyze the essential hydrolysis of adenine from 6-amino-6-deoxyfutalosine to form dehypoxanthinylfutalosine, a menaquinone precursor. The substrate specificity of CjMTAN is demonstrated to include 6-amino-6-deoxyfutalosine, 5'-methylthioadenosine, S-adenosylhomocysteine, adenosine, and 5'-deoxyadenosine. These activities span the catalytic specificities for the role of bacterial MTANs in menaquinone synthesis, quorum sensing, and S-adenosylmethionine recycling. We determined inhibition constants for potential transition-state analogues of CjMTAN. The best of these compounds have picomolar dissociation constants and were slow-onset tight-binding inhibitors. The most potent CjMTAN transition-state analogue inhibitors inhibited C. jejuni growth in culture at low micromolar concentrations, similar to gentamicin. The crystal structure of apoenzyme C. jejuni MTAN was solved at 1.25 A, and five CjMTAN complexes with transition-state analogues were solved at 1.42 to 1.95 A resolution. Inhibitor binding induces a loop movement to create a closed catalytic site with Asp196 and Ile152 providing purine leaving group activation and Arg192 and Glu12 activating the water nucleophile. With inhibitors bound, the interactions of the 4'-alkylthio or 4'-alkyl groups of this inhibitor family differ from the Escherichia coli MTAN structure by altered protein interactions near the hydrophobic pocket that stabilizes 4'-substituents of transition-state analogues. These CjMTAN inhibitors have potential as specific antibiotic candidates against C. jejuni.
Transition-State Analogues of Campylobacter jejuni 5'-Methylthioadenosine Nucleosidase.,Ducati RG, Harijan RK, Cameron SA, Tyler PC, Evans GB, Schramm VL ACS Chem Biol. 2018 Oct 19. doi: 10.1021/acschembio.8b00781. PMID:30339406[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li X, Apel D, Gaynor EC, Tanner ME. 5'-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni. J Biol Chem. 2011 Jun 3;286(22):19392-8. PMID:21489995 doi:10.1074/jbc.M111.229781
- ↑ Ducati RG, Harijan RK, Cameron SA, Tyler PC, Evans GB, Schramm VL. Transition-State Analogues of Campylobacter jejuni 5'-Methylthioadenosine Nucleosidase. ACS Chem Biol. 2018 Oct 19. doi: 10.1021/acschembio.8b00781. PMID:30339406 doi:http://dx.doi.org/10.1021/acschembio.8b00781
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