5d3z | pdb_00005d3z

Crystal structure of the thioesterase domain of deoxyerythronolide B synthase in complex with a small phosphonate inhibitor

spinqualitylabelsall models 5d3z, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d3z is a 1 chain structure with sequence from "actinomyces_erythreus"_(sic)_waksman_1923 "actinomyces erythreus" (sic) waksman 1923. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1PE, 57H, CA Gene: eryA ("Actinomyces erythreus" (sic) Waksman 1923) Activity: 6-deoxyerythronolide-B synthase, with EC number 2.3.1.94 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 6-deoxyerythronolide B synthase 3D structures

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