Wesley R. Harris
Professor
Harris joined the UM-St. Louis faculty in the Fall of 1988. He
received both his B.S. and his Ph.D. from Texas A&M University,
and was a Postdoctoral Associate at the University of California-Berkeley.
Prior to coming to St. Louis, he held faculty positions at the
University of California at Davis and the University of Idaho.
wharris@umsl.edu
Office: B320
Phone: (314) 516-5331
Fax: (314) 516-5342
Research
Interests
The insolubility of Fe3+ at physiological pH requires that organisms
transport this essential nutrient as a metal chelate. The transport
agent in mammals is the serum protein transferrin. Several aspects of
transferrin chemistry are being studied by Dr. Harris' group. One is
the kinetics of iron release to low molecular weight chelating agents.
The mechanism for this reaction is very complex. There appear to be
two pathways for iron release, and the relative importance of each pathway
varies among different types of ligands. The reaction rates are also
strongly affected by the binding of inorganic anions to an allosteric
regulatory site on the protein. This research is relevant to normal
iron metabolism and to the search for an effective drug for treating
iron toxicity.
In addition to its role in iron metabolism, transferrin also acts as
the primary transport agent for a variety of toxic and therapeutic metal
ions. Dr. Harris group has been heavily involved in evaluating the role
of transferrin in the serum transport of Al3+ . Studies are being conducted
on the binding of aluminum by serum chelating agents, on the exchange
of aluminum between transferrin and low molecular weight ligands, and
on computer models for the speciation of Al in serum and cerebral spinal
fluid.
Many of the current studies on transferrin involve the use of recombinant
transferrin and single point mutations of transferrin. These studies
involve collaborations with molecular biologists, who produce specific
mutants for chemical studies. These collaborative efforts now make it
possible to evaluate the influence of specific amino acid side chains
on metal binding affinities and the rates of metal exchange.
The Harris group has had a longstanding interest in the transferrin
binding affinities of different metal ions. Now that there is a significant
data base of binding affinities available, this research is focusing
more on evaluating the specific molecular factors that govern metal
binding affinity and selectivity. This includes the development of acid-base
parameters for the protein and selected metal ions that will enable
one to predict the transferrin binding constants for metals like Pu4+,
which are extremely hazardous and thus difficult to study directly.
Selected Publications
"The influence of citrate, maltolate and fluoride on the gastrointestinal absorption of aluminum at a drinking water-relevant concentration: A Al-26 and C-14 study", Y. Zhou, W. R. Harris and R. A. Yokel, Journal of Inorganic Biochemistry 2008, 102 798.
"Borate Binding to Siderophores: Structure and Stability", W. R. Harris, S. A. Amin, F. C. Kuepper, D. H. Green and C. J. Carrano, J. Am. Chem. Soc. 2007, 129, 12263.
"Boron Binding by a Siderophore Isolated from Marine Bacteria Associated with the Toxic Dinoflagellate Gymnodinium catenatum", S. A. Amin, F. C. Kuepper, D. H. Green, W. R. Harris and C. J. Carrano, J. Am. Chem. Soc., 2007, 129, 478.
"Determination of the binding constant of terbium-transferrin", S. Abdollahi and W. R. Harris, Iran J. Chem. Chem Eng., 2006, 25, 45.
"Stability constants and multinuclear NMR measurements of phosphonic acid derivatives with aluminum in aqueous solutions", Z. Y. Hamada and W. R. Harris, Inorg. Chim. Acta., 2006, 359, 1135.
"Modeling and Separation-Detection Methods to Evaluate the Speciation of Metals for Toxicity Assessment", J. Caruso, Joseph, R. Wuilloud, J. Altamirano and W. R. Harris, J. Toxicol. Environ. Health, 2006, B9, 41.
"Effect of Ligand Structure on the Pathways for Iron Release from Human Serum Transferrin", C. E. Brook, W. R. Harris, C. D. Spilling, P. Wang, J. Harburn and S. Srisung, Inorg. Chem., 2005, 44, 5183.
"Release of iron from transferrin by phosphonocarboxylate and diphosphonate chelating agents", W. R. Harris, C. E. Brook, C. D. Spilling, S. Elleppan, P. Wang, M. Xin and J. Van Wyk, J. Inorg. Biochem., 2004, 98, 1824.
"Identification of possible kinetically significant anion-binding sites in human serum transferrin using molecular modeling strategies", E. A. Amin, W. R. Harris and W. J. Welsh, Biopolymers, 2004, 73, 205.
"An isocratic separation of underivatized gentamicin components, 1H NMR assignment and protonation pattern", W. Lesniak, J. McLaren, W. R. Harris, V. L. Pecoraro and J. Schacht, Carbohydrate Res., 2004, 338, 2853.
"Kinetics of Metal Ion Exchange between Citric Acid and Serum Transferrin", W. R. Harris, Z. Wang, C. E. Brook, B. Yang and A. Islam, Inorg. Chem, 2003, 42, 5880.
"Competition between transferrin and the serum ligands citrate and phosphate for the binding of aluminum", W. R. Harris, Z. Wang, and Y. Z. Hamada, Inorg. Chem, 2003, 42, 3262.
"Solution Chemistry of Copper(II)-Gentamicin Complexes: Relevance to Metal-Related Aminoglycoside Toxicity", W. Lesniak, W. R. Harris, J. Y. Kravitz, J. Schacht and V. L. Pecoraro, Inorg. Chem., 2003, 42, 1420.
"Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae", M. Guo, I. Harvey, W. Yang, L. Coghill, D. J. Campopiano, J. A. Parkinson, R. T. MacGillivray, W. R. Harris and P. J. Sadler, J. Biol. Chem., 2003, 278, 2490.
"A comparative study of aluminum(III), gallium(III), indium(III), and thallium(III) binding to human serum transferring", W. R. Harris and L. Messori, Coord. Chem. Rev., 2002, 228, 237.