5kp5

Crystal Structure of the Curacin Biosynthetic Pathway HMG Synthase

spinqualitylabelsall models 5kp5, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kp5 is a 1 chain structure with sequence from Lyngbya majuscula 3l. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 5kp6, 5kp7 Gene: LYNGBM3L_74540 (Lyngbya majuscula 3L) Activity: Hydroxymethylglutaryl-CoA synthase, with EC number 2.3.3.10 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Alkyl branching at the beta position of a polyketide intermediate is an important variation on canonical polyketide natural product biosynthesis. The branching enzyme, 3-hydroxy-3-methylglutaryl synthase (HMGS), catalyzes the aldol addition of an acyl donor to a beta-keto-polyketide intermediate acceptor. HMGS is highly selective for two specialized acyl carrier proteins (ACPs) that deliver the donor and acceptor substrates. The HMGS from the curacin A biosynthetic pathway (CurD) was examined to establish the basis for ACP selectivity. The donor ACP (CurB) had high affinity for the enzyme (Kd = 0.5 muM) and could not be substituted by the acceptor ACP. High-resolution crystal structures of HMGS alone and in complex with its donor ACP reveal a tight interaction that depends on exquisite surface shape and charge complementarity between the proteins. Selectivity is explained by HMGS binding to an unusual surface cleft on the donor ACP, in a manner that would exclude the acceptor ACP. Within the active site, HMGS discriminates between pre- and postreaction states of the donor ACP. The free phosphopantetheine (Ppant) cofactor of ACP occupies a conserved pocket that excludes the acetyl-Ppant substrate. In comparison with HMG-CoA (CoA) synthase, the homologous enzyme from primary metabolism, HMGS has several differences at the active site entrance, including a flexible-loop insertion, which may account for the specificity of one enzyme for substrates delivered by ACP and the other by CoA. Anatomy of the beta-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate.,Maloney FP, Gerwick L, Gerwick WH, Sherman DH, Smith JL Proc Natl Acad Sci U S A. 2016 Aug 29. pii: 201607210. PMID:27573844 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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