5exk | pdb_00005exk

Crystal structure of M. tuberculosis lipoyl synthase with 6-thiooctanoyl peptide intermediate

spinqualitylabelsall models 5exk, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5exk is a 12 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.86Å Ligands: 5AD, CL, IMD, IPA, MET, XOK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LIPA_MYCTU Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. Publication Abstract from PubMed Lipoyl synthase (LipA) catalyzes the insertion of two sulfur atoms at the unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the lipoyl cofactor. To activate its substrate for sulfur insertion, LipA uses a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of the reaction mechanism, especially the source of the sulfur, has been less clear. One controversial proposal involves the removal of sulfur from a second (auxiliary) [4Fe-4S] cluster on the enzyme, resulting in destruction of the cluster during each round of catalysis. Here, we present two high-resolution crystal structures of LipA from Mycobacterium tuberculosis: one in its resting state and one at an intermediate state during turnover. In the resting state, an auxiliary [4Fe-4S] cluster has an unusual serine ligation to one of the irons. After reaction with an octanoyllysine-containing 8-mer peptide substrate and 1 eq AdoMet, conditions that allow for the first sulfur insertion but not the second insertion, the serine ligand dissociates from the cluster, the iron ion is lost, and a sulfur atom that is still part of the cluster becomes covalently attached to C6 of the octanoyl substrate. This intermediate structure provides a clear picture of iron-sulfur cluster destruction in action, supporting the role of the auxiliary cluster as the sulfur source in the LipA reaction and describing a radical strategy for sulfur incorporation into completely unactivated substrates. Crystallographic snapshots of sulfur insertion by lipoyl synthase.,McLaughlin MI, Lanz ND, Goldman PJ, Lee KH, Booker SJ, Drennan CL Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9446-50. doi:, 10.1073/pnas.1602486113. Epub 2016 Aug 9. PMID:27506792 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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