2xz0
From Proteopedia
The Structure of the 2:1 (Partially Occupied) Complex Between Stearoyl Acyl Carrier Protein Desaturase from Ricinus Communis (Castor Bean) and Acyl Carrier Protein.
Structural highlights
FunctionSTAD_RICCO Converts stearoyl-ACP to oleoyl-ACP by introduction of a cis double bond between carbons Delta(9) and Delta(10) of the acyl chain. Publication Abstract from PubMedRegiospecific desaturation of long-chain saturated fatty acids has been described as approaching the limits of the discriminatory power of enzymes because the substrate entirely lacks distinguishing features close to the site of dehydrogenation. To identify the elusive mechanism underlying regioselectivity, we have determined two crystal structures of the archetypal Delta9 desaturase from castor in complex with acyl carrier protein (ACP), which show the bound ACP ideally situated to position C9 and C10 of the acyl chain adjacent to the diiron active site for Delta9 desaturation. Analysis of the structures and modeling of the complex between the highly homologous ivy Delta4 desaturase and ACP, identified a residue located at the entrance to the binding cavity, Asp280 in the castor desaturase (Lys275 in the ivy desaturase), which is strictly conserved within Delta9 and Delta4 enzymes but differs between them. We hypothesized that interaction between Lys275 and the phosphate of the pantetheine, seen in the ivy model, is key to positioning C4 and C5 adjacent to the diiron center for Delta4 desaturation. Mutating castor Asp280 to Lys resulted in a major shift from Delta9 to Delta4 desaturation. Thus, interaction between desaturase side-chain 280 and phospho-serine 38 of ACP, approximately 27 A from the site of double-bond formation, predisposes ACP binding that favors either Delta9 or Delta4 desaturation via repulsion (acidic side chain) or attraction (positively charged side chain), respectively. Understanding the mechanism underlying remote control of regioselectivity provides the foundation for reengineering desaturase enzymes to create designer chemical feedstocks that would provide alternatives to those currently obtained from petrochemicals. Remote control of regioselectivity in acyl-acyl carrier protein-desaturases.,Guy JE, Whittle E, Moche M, Lengqvist J, Lindqvist Y, Shanklin J Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16594-9. Epub 2011 Sep 19. PMID:21930947[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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