6kjp | pdb_00006kjp

Functional and structural insights into the unusual oxyanion hole-like geometry in macrolactin acyltransferase selective for dicarboxylic acyl donors

spinqualitylabelsall models 6kjp, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kjp is a 1 chain structure with sequence from Jeotgalibacillus marinus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.06Å Ligands: D9F, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0U1X4V6_9BACL Publication Abstract from PubMed Macrolactins (MLNs) are a class of important antimacular degeneration and antitumor agents. Malonylated/succinylated MLNs are even more important due to their efficacy in overcoming multi-drug-resistant bacteria. However, which enzyme catalyzes this reaction remains enigmatic. Herein, we deciphered a beta-lactamase homologue BmmI to be responsible for this step. BmmI could specifically attach C3-C5 alkyl acid thioesters onto 7-OH of MLN A and also exhibits substrate promiscuity toward acyl acceptors with different scaffolds. The crystal structure of BmmI covalently linked to the succinyl group and systematic mutagenesis highlighted the role of oxyanion holelike geometry in the recognition of carboxyl-terminated acyl donors. The engineering of this geometry expanded its substrate scope, with the R166A/G/Q variants recognizing up to C12 alkyl acid thioester. The structure of BmmI with acyl acceptor MLN A revealed the importance of Arg292 in the recognition of macrolide substrates. Moreover, the mechanism of the BmmI-catalyzed acyltransfer reaction was established, unmasking the deft role of Lys76 in governing acyl donors as well as catalysis. Our studies uncover the delicate mechanism underlying the substrate selectivity of acyltransferases, which would guide rational enzyme engineering for drug development. Structural Basis of Specificity for Carboxyl-Terminated Acyl Donors in a Bacterial Acyltransferase.,Xiao F, Dong S, Liu Y, Feng Y, Li H, Yun CH, Cui Q, Li W J Am Chem Soc. 2020 Sep 1. doi: 10.1021/jacs.0c07331. PMID:32803979 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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