4pr3
From Proteopedia
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==Crystal structure of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase== | ==Crystal structure of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase== | ||
| - | <StructureSection load='4pr3' size='340' side='right' caption='[[4pr3]], [[Resolution|resolution]] 2.61Å' scene=''> | + | <StructureSection load='4pr3' size='340' side='right'caption='[[4pr3]], [[Resolution|resolution]] 2.61Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[4pr3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PR3 OCA]. <br> | + | <table><tr><td colspan='2'>[[4pr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_melitensis_bv._1_str._16M Brucella melitensis bv. 1 str. 16M]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PR3 FirstGlance]. <br> |
| - | <b>[[Ligand|Ligands:]]</b> <scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.606Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4pr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pr3 OCA], [https://pdbe.org/4pr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pr3 RCSB], [https://www.ebi.ac.uk/pdbsum/4pr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pr3 ProSAT]</span></td></tr> | |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | </table> |
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q8YBL1_BRUME Q8YBL1_BRUME] | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH), a process that plays a key role in several metabolic pathways. Its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. Here, we report the crystal structure of BmMTAN in complex with its product adenine at a resolution of 2.6A determined by single-wavelength anomalous dispersion method. 11 key residues were mutated for kinetic characterization. Mutations of Tyr134 and Met144 resulted in the largest overall increase in Km, whereas mutagenesis of residues Glu18, Glu145 and Asp168 completely abolished activity. Glu145 and Asp168 were identified as active site residues essential for catalysis. The catalytic mechanism and implications of this structure for broad-based antibiotic design are discussed. | The prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH), a process that plays a key role in several metabolic pathways. Its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. Here, we report the crystal structure of BmMTAN in complex with its product adenine at a resolution of 2.6A determined by single-wavelength anomalous dispersion method. 11 key residues were mutated for kinetic characterization. Mutations of Tyr134 and Met144 resulted in the largest overall increase in Km, whereas mutagenesis of residues Glu18, Glu145 and Asp168 completely abolished activity. Glu145 and Asp168 were identified as active site residues essential for catalysis. The catalytic mechanism and implications of this structure for broad-based antibiotic design are discussed. | ||
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Crystal structure and biochemical studies of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.,Kang X, Zhao Y, Jiang D, Li X, Wang X, Wu Y, Chen Z, Zhang XC Biochem Biophys Res Commun. 2014 Apr 18;446(4):965-70. doi:, 10.1016/j.bbrc.2014.03.045. Epub 2014 Mar 20. PMID:24657441<ref>PMID:24657441</ref> | Crystal structure and biochemical studies of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.,Kang X, Zhao Y, Jiang D, Li X, Wang X, Wu Y, Chen Z, Zhang XC Biochem Biophys Res Commun. 2014 Apr 18;446(4):965-70. doi:, 10.1016/j.bbrc.2014.03.045. Epub 2014 Mar 20. PMID:24657441<ref>PMID:24657441</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 4pr3" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Brucella melitensis bv. 1 str. 16M]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Chen ZL]] |
| - | [[Category: | + | [[Category: Jiang DH]] |
| - | [[Category: | + | [[Category: Kang XS]] |
| - | [[Category: | + | [[Category: Li XM]] |
| - | [[Category: | + | [[Category: Zhang XC]] |
| - | [[Category: | + | [[Category: Zhao Y]] |
Current revision
Crystal structure of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
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