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Publication Abstract from PubMed

Acyl carrier proteins (ACPs) play crucial roles in the biosynthesis of fatty acids, non-ribosomal polypeptides and polyketides. The three-dimensional NMR structure of Leishmania major holo-LmACP, belonging to the type II pathway, has been reported previously, but the structure of its apo-form and its conformational differences with the holo-form remain to be explored. Here we report the crystal structures of apo-LmACP (wild-type and S37A mutant) at 2.0A resolution and compare their key features with the structures of holo-LmACP (wild-type) and other type II ACPs from Escherichia coli and Plasmodium falciparum. The crystal structure of apo-LmACP, which is homologous to other type II ACPs, displays some key structural rearrangements as compared to its holo-structure. Contrary to holo-form, which exists predominantly as a monomer, the apo-form exists as a mixture of monomeric and dimeric population in solution. In contrast to the closed structure of apo-LmACP, holo-LmACP structure was observed in an open conformation as a result of reorganization of specific helices and loops. We propose that the structural changes exhibited by LmACP occur due to the attachment of the phosphopantetheine arm and may be a prerequisite for the initiation of fatty acid synthesis. The movement of helix 3 may also play a role in the dissociation of holo-LmACP from its cognate enzymes of the FAS II pathway.

A conformational switch from a closed apo- to an open holo-form equips the acyl carrier protein for acyl chain accommodation.,Arya R, Sharma B, Dhembla C, Pal RK, Patel AK, Sundd M, Ghosh B, Makde RD, Kundu S Biochim Biophys Acta Proteins Proteom. 2018 Dec 10;1867(3):163-174. doi:, 10.1016/j.bbapap.2018.12.001. PMID:30543875^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.