5hv8: Difference between revisions
New page: '''Unreleased structure''' The entry 5hv8 is ON HOLD Authors: Vance, S, Tkachenko, O, Thomas, B, Bassuni, M, Hong, H, Nietlispach, D, Broadhurst, RW Description: Solution structure of ... |
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The | ==Solution structure of an octanoyl- loaded acyl carrier protein domain from module MLSA2 of the mycolactone polyketide synthase.== | ||
<StructureSection load='5hv8' size='340' side='right'caption='[[5hv8]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hv8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_ulcerans Mycobacterium ulcerans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HV8 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=66S:S-[2-({N-[(2R)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-BETA-ALANYL}AMINO)ETHYL]+OCTANETHIOATE'>66S</scene></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=5hv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hv8 OCA], [https://pdbe.org/5hv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hv8 RCSB], [https://www.ebi.ac.uk/pdbsum/5hv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hv8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6MZA5_MYCUA Q6MZA5_MYCUA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type I modular polyketide synthases (PKSs) produce polyketide natural products by passing a growing acyl substrate chain between a series of enzyme domains housed within a gigantic multifunctional polypeptide assembly. Throughout each round of chain extension and modification reactions, the substrate stays covalently linked to an acyl carrier protein (ACP) domain. In the present study we report on the solution structure and dynamics of an ACP domain excised from MLSA2, module 9 of the PKS system that constructs the macrolactone ring of the toxin mycolactone, cause of the tropical disease Buruli ulcer. After modification ofapoACP with 4'-phosphopantetheine (Ppant) to create theholoform,(15)N nuclear spin relaxation and paramagnetic relaxation enhancement (PRE) experiments suggest that the prosthetic group swings freely. The minimal chemical shift perturbations displayed by Ppant-attached C3and C4acyl chains imply that these substrate-mimics remain exposed to solvent at the end of a flexible Ppant arm. By contrast, hexanoyl and octanoyl chains yield much larger chemical shift perturbations, indicating that they interact with the surface of the domain. The solution structure of octanoyl-ACP shows the Ppant arm bending to allow the acyl chain to nestle into a nonpolar pocket, whereas the prosthetic group itself remains largely solvent exposed. Although the highly reduced octanoyl group is not a natural substrate for the ACP from MLSA2, similar presentation modes would permit partner enzyme domains to recognize an acyl group while it is bound to the surface of its carrier protein, allowing simultaneous interactions with both the substrate and the ACP. | |||
Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.,Vance S, Tkachenko O, Thomas B, Bassuni M, Hong H, Nietlispach D, Broadhurst W Biochem J. 2016 Apr 15;473(8):1097-110. doi: 10.1042/BCJ20160041. Epub 2016 Feb, 26. PMID:26920023<ref>PMID:26920023</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5hv8" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium ulcerans]] | |||
[[Category: Bassuni M]] | |||
[[Category: Broadhurst RW]] | |||
[[Category: Hong H]] | |||
[[Category: Nietlispach D]] | |||
[[Category: Thomas B]] | |||
[[Category: Tkachenko O]] | |||
[[Category: Vance S]] | |||
Latest revision as of 13:54, 16 August 2023
Solution structure of an octanoyl- loaded acyl carrier protein domain from module MLSA2 of the mycolactone polyketide synthase.Solution structure of an octanoyl- loaded acyl carrier protein domain from module MLSA2 of the mycolactone polyketide synthase.
Structural highlights
FunctionPublication Abstract from PubMedType I modular polyketide synthases (PKSs) produce polyketide natural products by passing a growing acyl substrate chain between a series of enzyme domains housed within a gigantic multifunctional polypeptide assembly. Throughout each round of chain extension and modification reactions, the substrate stays covalently linked to an acyl carrier protein (ACP) domain. In the present study we report on the solution structure and dynamics of an ACP domain excised from MLSA2, module 9 of the PKS system that constructs the macrolactone ring of the toxin mycolactone, cause of the tropical disease Buruli ulcer. After modification ofapoACP with 4'-phosphopantetheine (Ppant) to create theholoform,(15)N nuclear spin relaxation and paramagnetic relaxation enhancement (PRE) experiments suggest that the prosthetic group swings freely. The minimal chemical shift perturbations displayed by Ppant-attached C3and C4acyl chains imply that these substrate-mimics remain exposed to solvent at the end of a flexible Ppant arm. By contrast, hexanoyl and octanoyl chains yield much larger chemical shift perturbations, indicating that they interact with the surface of the domain. The solution structure of octanoyl-ACP shows the Ppant arm bending to allow the acyl chain to nestle into a nonpolar pocket, whereas the prosthetic group itself remains largely solvent exposed. Although the highly reduced octanoyl group is not a natural substrate for the ACP from MLSA2, similar presentation modes would permit partner enzyme domains to recognize an acyl group while it is bound to the surface of its carrier protein, allowing simultaneous interactions with both the substrate and the ACP. Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.,Vance S, Tkachenko O, Thomas B, Bassuni M, Hong H, Nietlispach D, Broadhurst W Biochem J. 2016 Apr 15;473(8):1097-110. doi: 10.1042/BCJ20160041. Epub 2016 Feb, 26. PMID:26920023[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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