2luz

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Solution NMR Structure of CalU16 from Micromonospora echinospora, Northeast Structural Genomics Consortium (NESG) Target MiR12Solution NMR Structure of CalU16 from Micromonospora echinospora, Northeast Structural Genomics Consortium (NESG) Target MiR12

Structural highlights

2luz is a 1 chain structure with sequence from Micromonospora echinospora. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8KNE9_MICEC

Publication Abstract from PubMed

Calicheamicin gamma1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis and biochemical study, several genes in the biosynthetic gene cluster of 1 remain functionally unassigned. Using a structural genomics approach and biochemical characterization, two proteins encoded by genes from the 1 biosynthetic gene cluster assigned as "unknowns", CalU16 and CalU19, were characterized. Structure analysis revealed that they possess the STeroidogenic Acute Regulatory protein related lipid Transfer (START) domain known mainly to bind and transport lipids and previously identified as the structural signature of the enediyne self-resistance protein CalC. Subsequent study revealed calU16 and calU19 to confer resistance to 1, and reminiscent of the prototype CalC, both CalU16 and CalU19 were cleaved by 1 in vitro. Through site-directed mutagenesis and mass spectrometry, we identified the site of cleavage in each protein and characterized their function in conferring resistance against 1. This report emphasizes the importance of structural genomics as a powerful tool for the functional annotation of unknown proteins.

Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19.,Elshahawi SI, Ramelot TA, Seetharaman J, Chen J, Singh S, Yang Y, Pederson K, Kharel MK, Xiao R, Lew S, Yennamalli RM, Miller MD, Wang F, Tong L, Montelione GT, Kennedy MA, Bingman CA, Zhu H, Phillips GN Jr, Thorson JS ACS Chem Biol. 2014 Aug 13. PMID:25079510[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Elshahawi SI, Ramelot TA, Seetharaman J, Chen J, Singh S, Yang Y, Pederson K, Kharel MK, Xiao R, Lew S, Yennamalli RM, Miller MD, Wang F, Tong L, Montelione GT, Kennedy MA, Bingman CA, Zhu H, Phillips GN Jr, Thorson JS. Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19. ACS Chem Biol. 2014 Aug 13. PMID:25079510 doi:http://dx.doi.org/10.1021/cb500327m
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