2l65 | pdb_00002l65

HADDOCK calculated model of the complex of the resistance protein CalC and Calicheamicin-Gamma

spinqualitylabelsall models 2l65, 4 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2l65 is a 1 chain structure with sequence from micromonospora_purpurea_luedemann_and_brodsky_1964_(approved_lists_1980) Atcc 15835 micromonospora purpurea luedemann and brodsky 1964 (approved lists 1980). This structure supersedes the now removed PDB entry 2gkc. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DSR, HIB, MRP, MTC, DAG NonStd Res: EMP Related: 1zxf, 2pik Gene: calC (ATCC 15835 Micromonospora purpurea Luedemann and Brodsky 1964 (Approved Lists 1980)) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The recent discovery of the first "self-sacrifice" mechanism for bacterial resistance to the enediyne antitumor antibiotics, where enediyne-induced proteolysis of the resistance protein CalC inactivates both the highly reactive metabolite and the resistance protein, revealed yet another ingenious bacterial mechanism for controlling reactive metabolites. As reported herein, the first 3D structures of CalC and CalC in complex with calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute regulatory protein (StAR)-related transfer (START) domain superfamily. In contrast to previous studies of proteins known to bind DNA-damaging natural products ( e.g ., bleomycins, mitomycins, and nine-membered chromoprotein enediynes), this is the first demonstrated involvement of a START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM in complex with CalC is positioned for direct hydrogen abstraction from Gly113 to initiate the oxidative proteolysis-based resistance mechanism. These structural studies also illuminate, for the first time, a small DNA-binding region within CalC that may serve to localize CalC to the enediyne target (DNA). Given the role of START domains in nuclear/cytosolic transport and translocation, this structural study also may implicate START domains as post-endocytotic intracellular chaperones for enediyne-based therapeutics such as MyloTarg. Structural insight into the self-sacrifice mechanism of enediyne resistance.,Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL, Thorson JS ACS Chem Biol. 2006 Aug 22;1(7):451-60. PMID:17168523 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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