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| | <StructureSection load='3iob' size='340' side='right'caption='[[3iob]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='3iob' size='340' side='right'caption='[[3iob]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3iob]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IOB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3iob]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IOB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A4D:5-THIOADENOSINE'>A4D</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cov|3cov]], [[3cow|3cow]], [[3coy|3coy]], [[3coz|3coz]], [[1n2h|1n2h]], [[3ioc|3ioc]], [[3iod|3iod]], [[3ioe|3ioe]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A4D:5-THIOADENOSINE'>A4D</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT3707, MTCY07H7B.20, panC, Rv3602c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] </span></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=3iob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iob OCA], [https://pdbe.org/3iob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iob RCSB], [https://www.ebi.ac.uk/pdbsum/3iob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iob ProSAT]</span></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=3iob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iob OCA], [https://pdbe.org/3iob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iob RCSB], [https://www.ebi.ac.uk/pdbsum/3iob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iob ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PANC_MYCTU PANC_MYCTU]] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.<ref>PMID:11669627</ref>
| + | [https://www.uniprot.org/uniprot/PANC_MYCTU PANC_MYCTU] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.<ref>PMID:11669627</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pantoate--beta-alanine ligase]] | |
| - | [[Category: Abell, C]] | |
| - | [[Category: Ciulli, A]] | |
| - | [[Category: Scott, D E]] | |
| - | [[Category: Atp-binding]] | |
| - | [[Category: Drug design]] | |
| - | [[Category: Dynamic combinatorial chemistry]] | |
| - | [[Category: Enzyme]] | |
| - | [[Category: Fragment-based]] | |
| - | [[Category: Inhibitor]] | |
| - | [[Category: Ligase]] | |
| - | [[Category: Magnesium]] | |
| - | [[Category: Metal-binding]] | |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Nucleotide-binding]] | + | [[Category: Abell C]] |
| - | [[Category: Pantothenate biosynthesis]] | + | [[Category: Ciulli A]] |
| | + | [[Category: Scott DE]] |
| Structural highlights
Function
PANC_MYCTU Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.[1]
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 PubMed
A new strategy that combines the concepts of fragment-based drug design and dynamic combinatorial chemistry (DCC) for targeting adenosine recognition sites on enzymes is reported. We demonstrate the use of 5'-deoxy-5'-thioadenosine as a noncovalent anchor fragment in dynamic combinatorial libraries templated by Mycobacterium tuberculosis pantothenate synthetase. A benzyl disulfide derivative was identified upon library analysis by HPLC. Structural and binding studies of protein-ligand complexes by X-ray crystallography and isothermal titration calorimetry informed the subsequent optimisation of the DCC hit into a disulfide containing the novel meta-nitrobenzyl fragment that targets the pantoate binding site of pantothenate synthetase. Given the prevalence of adenosine-recognition motifs in enzymes, our results provide a proof-of-concept for using this strategy to probe adjacent pockets for a range of adenosine binding enzymes, including other related adenylate-forming ligases, kinases, and ATPases, as well as NAD(P)(H), CoA and FAD(H2) binding proteins.
A fragment-based approach to probing adenosine recognition sites by using dynamic combinatorial chemistry.,Scott DE, Dawes GJ, Ando M, Abell C, Ciulli A Chembiochem. 2009 Nov 23;10(17):2772-9. PMID:19827080[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zheng R, Blanchard JS. Steady-state and pre-steady-state kinetic analysis of Mycobacterium tuberculosis pantothenate synthetase. Biochemistry. 2001 Oct 30;40(43):12904-12. PMID:11669627
- ↑ Scott DE, Dawes GJ, Ando M, Abell C, Ciulli A. A fragment-based approach to probing adenosine recognition sites by using dynamic combinatorial chemistry. Chembiochem. 2009 Nov 23;10(17):2772-9. PMID:19827080 doi:10.1002/cbic.200900537
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