PDBsum entry 2l65

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Structural genomics, unknown function PDB id
Jmol PyMol
Protein chain
155 a.a. *
* Residue conservation analysis
PDB id:
Name: Structural genomics, unknown function
Title: Haddock calculated model of the complex of the resistance pr and calicheamicin-gamma
Structure: Calc. Chain: a. Fragment: sequence database residues 27-181. Engineered: yes
Source: Micromonospora echinospora. Organism_taxid: 1877. Gene: calc. Expressed in: escherichia coli. Expression_system_taxid: 469008.
NMR struc: 4 models
Authors: S.Singh,J.L.Markley,J.S.Thorson,Center For Eukaryotic Struct Genomics (Cesg)
Key ref: S.Singh et al. (2006). Structural insight into the self-sacrifice mechanism of enediyne resistance. ACS Chem Biol, 1, 451-460. PubMed id: 17168523 DOI: 10.1021/cb6002898
15-Nov-10     Release date:   02-Mar-11    
Supersedes: 2gkc
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Protein chain
Pfam   ArchSchema ?
Q8KNF0  (Q8KNF0_MICEC) -  CalC
181 a.a.
155 a.a.
Key:    PfamA domain  Secondary structure


DOI no: 10.1021/cb6002898 ACS Chem Biol 1:451-460 (2006)
PubMed id: 17168523  
Structural insight into the self-sacrifice mechanism of enediyne resistance.
S.Singh, M.H.Hager, C.Zhang, B.R.Griffith, M.S.Lee, K.Hallenga, J.L.Markley, J.S.Thorson.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20818668 J.L.Stark, K.A.Mercier, G.A.Mueller, T.B.Acton, R.Xiao, G.T.Montelione, and R.Powers (2010).
Solution structure and function of YndB, an AHSA1 protein from Bacillus subtilis.
  Proteins, 78, 3328-3340.  
20466807 M.van Dijk, and A.M.Bonvin (2010).
Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance.
  Nucleic Acids Res, 38, 5634-5647.  
20336235 Z.X.Liang (2010).
Complexity and simplicity in the biosynthesis of enediyne natural products.
  Nat Prod Rep, 27, 499-528.  
18561189 J.G.McCoy, H.D.Johnson, S.Singh, C.A.Bingman, I.K.Lei, J.S.Thorson, and G.N.Phillips (2009).
Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway.
  Proteins, 74, 50-60.
PDB code: 3buj
19493340 K.S.Makarova, Y.I.Wolf, and E.V.Koonin (2009).
Comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes.
  Biol Direct, 4, 19.  
18922149 C.Radauer, P.Lackner, and H.Breiteneder (2008).
The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands.
  BMC Evol Biol, 8, 286.  
18721755 C.Zhang, E.Bitto, R.D.Goff, S.Singh, C.A.Bingman, B.R.Griffith, C.Albermann, G.N.Phillips, and J.S.Thorson (2008).
Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis.
  Chem Biol, 15, 842-853.
PDB codes: 3d0q 3d0r
18497896 M.S.Butler (2008).
Natural products to drugs: natural product-derived compounds in clinical trials.
  Nat Prod Rep, 25, 475-516.  
18328078 Q.Gao, and J.S.Thorson (2008).
The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710.
  FEMS Microbiol Lett, 282, 105-114.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.