8ee1: Difference between revisions
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==KS-AT didomain from module 2 of the 6-deoxyerythronolide B synthase in complex with antibody fragment AA5== | |||
<StructureSection load='8ee1' size='340' side='right'caption='[[8ee1]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ee1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharopolyspora_erythraea Saccharopolyspora erythraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EE1 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]] 2.7Å</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=8ee1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ee1 OCA], [https://pdbe.org/8ee1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ee1 RCSB], [https://www.ebi.ac.uk/pdbsum/8ee1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ee1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ERYA1_SACER ERYA1_SACER] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:37184546</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8ee1" style="background-color:#fffaf0;"></div> | ||
[[Category: Brodsky | == References == | ||
[[Category: Guzman | <references/> | ||
[[Category: Khosla | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Saccharopolyspora erythraea]] | |||
[[Category: Brodsky KL]] | |||
[[Category: Cogan DP]] | |||
[[Category: Guzman KM]] | |||
[[Category: Khosla C]] | |||
[[Category: Mathews II]] | |||