3dp9: Difference between revisions
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<StructureSection load='3dp9' size='340' side='right'caption='[[3dp9]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3dp9' size='340' side='right'caption='[[3dp9]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dp9]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3dp9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DP9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIG:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-[(BUTYLSULFANYL)METHYL]PYRROLIDIN-3-OL'>BIG</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BIG:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-[(BUTYLSULFANYL)METHYL]PYRROLIDIN-3-OL'>BIG</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Adenosylhomocysteine_nucleosidase Adenosylhomocysteine nucleosidase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dp9 OCA], [https://pdbe.org/3dp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dp9 RCSB], [https://www.ebi.ac.uk/pdbsum/3dp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dp9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/MTNN_VIBCH MTNN_VIBCH]] 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.[HAMAP-Rule:MF_01684] | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Revision as of 11:04, 9 February 2022
Crystal structure of Vibrio cholerae 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with butylthio-DADMe-Immucillin ACrystal structure of Vibrio cholerae 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with butylthio-DADMe-Immucillin A
Structural highlights
Function[MTNN_VIBCH] 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.[HAMAP-Rule:MF_01684] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogs MT-DADMe-Immucillin-A, EtT-DADMe-Immucillin-A and BuT-DADMe-Immucillin-A are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with equilibrium dissociation constants of 73, 70 and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-Immucillin-A revealed interactions contributing to the high affinity. We found that in V. cholerae cells, these compounds are potent MTAN inhibitors with IC(50) values of 27, 31 and 6 nM for MT-, EtT- and BuT-DADMe-Immucillin-A, respectively; the compounds disrupt autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-Immucillin-A also inhibited autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC(50) values of 600 and 125 nM, respectively. BuT-DADMe-Immucillin-A inhibition of autoinducer-2 production in both strains persisted for several generations and caused reduction in biofilm formation. These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design. Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.,Gutierrez JA, Crowder T, Rinaldo-Matthis A, Ho MC, Almo SC, Schramm VL Nat Chem Biol. 2009 Apr;5(4):251-7. Epub 2009 Mar 8. PMID:19270684[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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