FTIR Analysis of Protein Secondary Structure: Albumin, abundant in blood, is a major transport protein for endogenous and exogenous components of the circulatory system.   X-ray diffraction studies revealed the heart shape of this molecule composed of three homologous domains.    Interactions of the domains of this highly helical (66%) protein  stabilized by numerous disulfide bonds are loosened by manipulation of the solution environment.  In general, the broad spectrum of drugs, such as aspirin, diazapam, and AZT, traveling the circulatory system bind to one of two sites located in helical  subdomains IIA and IIIA.   We are using FTIR,  sensitive to changes in protein secondary  structure, to monitor alterations in structure in response to changing solution conditions and drug binding.

FTNMR Studies of Ligand Binding to Proteins:
A) Preliminary results of two dimensional H1 noesy experiments of nucleotide bound to tubulin when subjected to molecular modeling analysis indicate a predominantly anti-oriented guanine base coupled to an envelope conformation of ribose.  This ribose conformation differs from the twisted forms commonly found in nucleic acids.   Current investigations focus on the conformation of GTP, free and unbound in solution. 

B) Noesy experiments are used to investigate the conformation of drugs bound to albumin with attention to benzodiazepines and nucleotides.  Although Valium is the most widely known benzodiazepine, this class of pharmaceuticals have a wide spectrum of biological activity, such as anticonvulsant and anti HIV reverse transcriptase action.    Although the benzodiazepines and nucleotides , such as AZT, nominally bind to the same IIIA, they  are substantially different structures expected to have unique bound conformations that distinguishable interactions with amino acid residues within the general binding site.

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