5d3k: Difference between revisions
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''' | ==Crystal structure of the thioesterase domain of deoxyerythronolide B synthase== | ||
<StructureSection load='5d3k' size='340' side='right' caption='[[5d3k]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5d3k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D3K FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5d2r|5d2r]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/6-deoxyerythronolide-B_synthase 6-deoxyerythronolide-B synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.94 2.3.1.94] </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=5d3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3k OCA], [http://pdbe.org/5d3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d3k RCSB], [http://www.ebi.ac.uk/pdbsum/5d3k PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type I polyketide synthases (PKSs) are giant multidomain proteins that synthesize many therapeutics and other natural products. The synthesis proceeds by a thiotemplate mechanism whereby intermediates are covalently attached to the PKS. The release of the final polyketide is catalyzed by the terminal thioesterase (TE) domain through hydrolysis, transesterification, or macrocyclization. The PKS 6-deoxyerythronolide B synthase (DEBS) produces the 14-membered macrolide core of the clinically important antibiotic erythromycin. The TE domain of DEBS (DEBS TE) has well-established, empirically-defined specificities for hydrolysis or macrocyclization of native and modified substrates. We present efforts towards understanding the structural basis for the specificity of the thioesterase reaction in DEBS TE using a set of novel diphenyl alkylphosphonates, which mimic substrates that are specifically cyclized or hydrolyzed by DEBS TE. We have determined structures of a new construct of DEBS TE alone at 1.7A, and DEBS TE bound with a simple allylphosphonate at 2.1A resolution. Other, more complex diphenyl alkylphosphonates inhibit DEBS TE, but we were unable to visualize these faithful cyclization analogs in complex with DEBS TE. This work represents a first step towards using DEBS TE complexed with sophisticated substrate analogs to decipher the specificity determinants in this important reaction. | |||
Towards a characterization of the structural determinants of specificity in the macrocyclizing thioesterase for deoxyerythronolide B biosynthesis.,Argyropoulos P, Bergeret F, Pardin C, Reimer JM, Pinto A, Boddy CN, Martin Schmeing T Biochim Biophys Acta. 2015 Nov 22. pii: S0304-4165(15)00324-4. doi:, 10.1016/j.bbagen.2015.11.007. PMID:26592346<ref>PMID:26592346</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5d3k" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: 6-deoxyerythronolide-B synthase]] | |||
[[Category: Argyropoulos, P]] | |||
[[Category: Bergeret, F]] | [[Category: Bergeret, F]] | ||
[[Category: Boddy, C N]] | |||
[[Category: Schmeing, T M]] | |||
[[Category: Hydrolase]] | |||
[[Category: Thioesterase domaine alpha / beta hydrolase fold deoxyerythronolide b synthase]] | |||
Revision as of 16:40, 9 December 2015
Crystal structure of the thioesterase domain of deoxyerythronolide B synthaseCrystal structure of the thioesterase domain of deoxyerythronolide B synthase
Structural highlights
Publication Abstract from PubMedType I polyketide synthases (PKSs) are giant multidomain proteins that synthesize many therapeutics and other natural products. The synthesis proceeds by a thiotemplate mechanism whereby intermediates are covalently attached to the PKS. The release of the final polyketide is catalyzed by the terminal thioesterase (TE) domain through hydrolysis, transesterification, or macrocyclization. The PKS 6-deoxyerythronolide B synthase (DEBS) produces the 14-membered macrolide core of the clinically important antibiotic erythromycin. The TE domain of DEBS (DEBS TE) has well-established, empirically-defined specificities for hydrolysis or macrocyclization of native and modified substrates. We present efforts towards understanding the structural basis for the specificity of the thioesterase reaction in DEBS TE using a set of novel diphenyl alkylphosphonates, which mimic substrates that are specifically cyclized or hydrolyzed by DEBS TE. We have determined structures of a new construct of DEBS TE alone at 1.7A, and DEBS TE bound with a simple allylphosphonate at 2.1A resolution. Other, more complex diphenyl alkylphosphonates inhibit DEBS TE, but we were unable to visualize these faithful cyclization analogs in complex with DEBS TE. This work represents a first step towards using DEBS TE complexed with sophisticated substrate analogs to decipher the specificity determinants in this important reaction. Towards a characterization of the structural determinants of specificity in the macrocyclizing thioesterase for deoxyerythronolide B biosynthesis.,Argyropoulos P, Bergeret F, Pardin C, Reimer JM, Pinto A, Boddy CN, Martin Schmeing T Biochim Biophys Acta. 2015 Nov 22. pii: S0304-4165(15)00324-4. doi:, 10.1016/j.bbagen.2015.11.007. PMID:26592346[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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