5uzl

From Proteopedia

Brassica napus DGAT1 exosite

Structural highlights

5uzl is a 1 chain structure with sequence from Brassica napus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

K9LL63_BRANA

Publication Abstract from PubMed

Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT11-113) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an alpha-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis.

Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.,Caldo KMP, Acedo JZ, Panigrahi R, Vederas JC, Weselake RJ, Lemieux MJ Plant Physiol. 2017 Oct;175(2):667-680. doi: 10.1104/pp.17.00934. Epub 2017 Aug, 21. PMID:28827454^[1]

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

References

↑ Caldo KMP, Acedo JZ, Panigrahi R, Vederas JC, Weselake RJ, Lemieux MJ. Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors. Plant Physiol. 2017 Oct;175(2):667-680. doi: 10.1104/pp.17.00934. Epub 2017 Aug, 21. PMID:28827454 doi:http://dx.doi.org/10.1104/pp.17.00934