Abstract

The structure of CoBLM bound to d(CCAGTACTGG) has been solved (J. Am. Chem. Soc. 1996, 118, 1281-1294). Binding results form partial intercalation of the bithiazole tail 8' to the sight of DNA cleavage. The hosts for sequence selectivity of cleavage, at G 3' to pyrimidine has been identified to involve hydrogen bonding interaction between the N3 and 2 amino group of G and the amino group and N3 of the pyrimidine of CoBLM. The hydrogen of the hydroperoxide of CoBLM has been identified and modeling reveals it is located 2.5 ? from the hydrogen atom of the DNA that is abstracted. We have obtained data on phleomycin and deglyco BLMs (green and brown forms) bound to this sequence. We have also acquired data for CoBLM green and brown bound to a """"""""hot spot"""""""" for double-stranded cleavage. The mode of binding and basis of recognition is very similar to that observed with d(CCAGGCCTGG), although we are still returning the model. We will look at a variety of deglyco mutant BLMs, provided by Boger's laboratory at Scripps, to try to understand how a single molecule of BLM can effect the double-stranded breaks.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-21
Application #
5221934
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

Showing the most recent 10 out of 12 publications