6aym: Difference between revisions
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<StructureSection load='6aym' size='340' side='right' caption='[[6aym]], [[Resolution|resolution]] 1.25Å' scene=''> | <StructureSection load='6aym' size='340' side='right' caption='[[6aym]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6aym]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYM FirstGlance]. <br> | <table><tr><td colspan='2'>[[6aym]] 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=6AYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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='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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aym OCA], [http://pdbe.org/6aym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aym RCSB], [http://www.ebi.ac.uk/pdbsum/6aym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aym 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=6aym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aym OCA], [http://pdbe.org/6aym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aym RCSB], [http://www.ebi.ac.uk/pdbsum/6aym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aym ProSAT]</span></td></tr> | ||
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== 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] | [[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] | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:30339406</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6aym" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Campylobacter fetus subsp. jejuni smibert 1974]] | |||
[[Category: Adenosylhomocysteine nucleosidase]] | [[Category: Adenosylhomocysteine nucleosidase]] | ||
[[Category: Almo, S C]] | [[Category: Almo, S C]] | ||
Revision as of 10:10, 31 October 2018
Crystal structure of Campylobacter jejuni 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN)Crystal structure of Campylobacter jejuni 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN)
Structural highlights
Function[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] Publication Abstract from PubMedCampylobacter 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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