4yml
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4yml is ON HOLD Authors: Cameron, S.A., Thomas, K., Almo, S.C., Schramm, V.L. Description: Crystal structure of Escherichia coli 5'-methylthioadeno...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Escherichia coli 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with (3S,4R)-methylthio-DADMe-Immucillin-A== | |
| + | <StructureSection load='4yml' size='340' side='right'caption='[[4yml]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4yml]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YML FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4F0:(3S,4R)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-[(METHYLSULFANYL)METHYL]PYRROLIDIN-3-OL'>4F0</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4yml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yml OCA], [https://pdbe.org/4yml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yml RCSB], [https://www.ebi.ac.uk/pdbsum/4yml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yml ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MTNN_ECOLI MTNN_ECOLI] 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. Can also use 5'-isobutylthioadenosine, 5'-n-butylthioadenosine, S-adenosyl-D-homocysteine, decarboxylated adenosylhomocysteine, deaminated adenosylhomocysteine and S-2-aza-adenosylhomocysteine as substrates.[HAMAP-Rule:MF_01684] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors. | ||
| - | + | Tight binding enantiomers of pre-clinical drug candidates.,Evans GB, Cameron SA, Luxenburger A, Guan R, Suarez J, Thomas K, Schramm VL, Tyler PC Bioorg Med Chem. 2015 Jul 30. pii: S0968-0896(15)00643-4. doi:, 10.1016/j.bmc.2015.07.059. PMID:26260335<ref>PMID:26260335</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Almo | + | <div class="pdbe-citations 4yml" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Schramm | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Almo SC]] | ||
| + | [[Category: Cameron SA]] | ||
| + | [[Category: Schramm VL]] | ||
| + | [[Category: Thomas K]] | ||
Current revision
Crystal structure of Escherichia coli 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with (3S,4R)-methylthio-DADMe-Immucillin-A
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