Ph.D., University of Adelaide
D.Sc., University of Adelaide
B.S., University of Adelaide
Office: Willamette Hall Room 376
Office Phone: 541-346-2572
Since his retirement Dr. Matthews does not have an active research group.
In the past our laboratory used X-ray crystallography, in concert with other techniques, to address some of the fundamental problems in biology: How do proteins spontaneously fold into their biologically active three-dimensional configurations? What determines the stability of these folded proteins? Can stability be improved? How do proteins interact with each other? How do proteins interact with DNA? How do enzymes interact with their substrates and act as catalysts?
We have used the lysozyme from bacteriophage T4 to define the contributions that different types of interaction make to the stability of proteins. One of the key findings is that the protein is, in general, very tolerant of amino acid replacement. This has permitted more challenging experiments such as the insertion or deletion of longer segments of the polypeptide chain. Such changes can be used to address a variety of questions regarding protein folding. It has recently become possible to monitor the behavior, including folding and catalysis, of single molecules. The wealth of information already available for T4 lysozyme makes it a very attractive subject for such studies and we are actively pursuing this new area.
Lysozymes with designed cavities are being used to test and to improve the effectiveness of docking programs designed to predict the optimal small-molecule that will bind to a given target site. Such sites are also being used to model the binding of general anesthetics.
We are also interested in the structural basis of DNA-protein interaction. Recent studies have focused on enzymes that are highly processive, i.e. they undergo multiple rounds of catalysis without dissociating from the substrate. In many, but not all cases, processivity can be achieved by having the enzyme completely enclose its substrate. In the case of lambda-exonuclease, for example, the enzyme forms a symmetrical toroid. For exonuclease I from E. coli, a toroid is also formed, but is by no means symmetrical (see figures).
Several years ago we determined the three-dimensional structure of Escherichia coli beta-galactosidase, one of the classic enzymes in molecular biology. As well as studies of the enzyme, per se, we are also using this system to try to understand, in detail, the response of protein crystals to flash-freezing, an increasingly common step in contemporary X-ray crystallography.
Other areas of interest include structure-function studies of the F- and V-type ATPases, as well as various peptidases including the thermostable zinc protease thermolysin, the cobalt-requiring methionine aminopeptidase from E. coli as well as the serine peptidases.
(pulled from pubmed)
(pulled from pubmed)