5te2
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5te2 is ON HOLD Authors: Maize, K.M., Eiden, C., Aldrich, C.C., Finzel, B.C. Description: Crystal structure of 7,8-diaminopelargonic acid synthase ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a mechanism-based inhibitor== | |
| + | <StructureSection load='5te2' size='340' side='right'caption='[[5te2]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5te2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_variant_bovis_AF2122/97 Mycobacterium tuberculosis variant bovis AF2122/97]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TE2 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7B9:[5-hydroxy-4-({[6-(3-hydroxypropyl)-4-oxo-1,4-dihydropyridin-3-yl]amino}methyl)-6-methylpyridin-3-yl]methyl+dihydrogen+phosphate'>7B9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5te2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5te2 OCA], [https://pdbe.org/5te2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5te2 RCSB], [https://www.ebi.ac.uk/pdbsum/5te2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5te2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BIOA_MYCBO BIOA_MYCBO] Catalyzes the transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mechanism-based inhibitors (MBIs) are widely employed in chemistry, biology, and medicine because of their exquisite specificity and sustained duration of inhibition. Optimization of MBIs is complicated because of time-dependent inhibition resulting from multistep inactivation mechanisms. The global kinetic parameters kinact and KI have been used to characterize MBIs, but they provide far less information than is commonly assumed, as shown by derivation and simulation of these parameters. We illustrate an alternative and more rigorous approach for MBI characterization through determination of the individual microscopic rate constants. Kinetic analysis revealed the rate-limiting step of inactivation of the PLP-dependent enzyme BioA by dihydro-(1,4)-pyridone 1. This knowledge was subsequently applied to rationally design a second-generation inhibitor scaffold with a nearly optimal maximum inactivation rate (0.48 min-1). | ||
| - | + | Rational Optimization of Mechanism-Based Inhibitors through Determination of the Microscopic Rate Constants of Inactivation.,Eiden CG, Maize KM, Finzel BC, Lipscomb JD, Aldrich CC J Am Chem Soc. 2017 May 31;139(21):7132-7135. doi: 10.1021/jacs.7b00962. Epub, 2017 May 18. PMID:28510452<ref>PMID:28510452</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5te2" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Aminotransferase 3D structures|Aminotransferase 3D structures]] |
| + | *[[7%2C8-diaminopelargonic acid synthase 3D structures|7%2C8-diaminopelargonic acid synthase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis variant bovis AF2122/97]] | ||
| + | [[Category: Aldrich CC]] | ||
| + | [[Category: Eiden C]] | ||
| + | [[Category: Finzel BC]] | ||
| + | [[Category: Maize KM]] | ||
Current revision
Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a mechanism-based inhibitor
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