4yml
From Proteopedia
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| - | ''' | + | ==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YML FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wkc|4wkc]], [[1y6q|1y6q]]</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=4yml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yml OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yml RCSB], [http://www.ebi.ac.uk/pdbsum/4yml PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: Almo, S | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Adenosylhomocysteine nucleosidase]] | ||
| + | [[Category: Almo, S C]] | ||
| + | [[Category: Cameron, S A]] | ||
| + | [[Category: Schramm, V L]] | ||
[[Category: Thomas, K]] | [[Category: Thomas, K]] | ||
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Hydrolase-hydrolase inhibitor complex]] |
Revision as of 13:29, 26 August 2015
Crystal structure of Escherichia coli 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with (3S,4R)-methylthio-DADMe-Immucillin-A
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