8ee0

KS-AT didomain from module 2 of the 6-deoxyerythronolide B synthase in complex with antibody fragment 1B2

spinqualitylabelsall models 8ee0, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ee0 is a 3 chain structure with sequence from Homo sapiens and Saccharopolyspora erythraea. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ERYA1_SACER Publication Abstract from PubMed Fragment antigen-binding domains of antibodies (F(ab)s) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of F(ab)s interrogating the structure and function of the ketosynthase-acyltransferase (KS-AT) core of Module 2 of the 6-deoxyerythronolide B synthase (DEBS). Two F(ab)s (AC2 and BB1) were identified to potently inhibit the catalytic activity of Module 2. Both AC2 and BB1 were found to modulate ACP-mediated reactions catalyzed by this module, albeit by distinct mechanisms. AC2 primarily affects the rate (k(cat)), whereas BB1 increases the K(M) of an ACP-mediated reaction. A third F(ab), AA5, binds to the KS-AT fragment of DEBS Module 2 without altering either parameter; it is phenotypically reminiscent of a previously characterized F(ab), 1B2, shown to principally recognize the N-terminal helical docking domain of DEBS Module 3. Crystal structures of AA5 and 1B2 bound to the KS-AT fragment of Module 2 were solved to 2.70 and 2.65 A resolution, respectively, and revealed entirely distinct recognition features of the two antibodies. The new tools and insights reported here pave the way toward advancing our understanding of the structure-function relationships of DEBS Module 2, arguably the most well-studied module of an assembly line PKS. Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase.,Guzman KM, Cogan DP, Brodsky KL, Soohoo AM, Li X, Sevillano N, Mathews II, Nguyen KP, Craik CS, Khosla C Biochemistry. 2023 Jun 6;62(11):1589-1593. doi: 10.1021/acs.biochem.3c00156. Epub , 2023 May 15. PMID:37184546 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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