Institute of Molecular Biology


Home | About | Faculty | Calendar | Facilities | Graduate program | Contact | Apply

This page is optimized for viewing with javascript.


Brian W. Matthews

Brian W. Matthews

Emeritus, Physics
Member, IMB

Ph.D., University of Adelaide
D.Sc., University of Adelaide
B.S., University of Adelaide

Email
Office: Willamette Hall Room 376
Office Phone: 541-346-2572

Loading profile for Brian W. Matthews

Research Interests

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).

matthews research matthews research Model (top) showing the presumed mode by which lambda-exonuclease encloses DNA and processively hydrolyzes one of the two strands. The figure on the bottom shows the structure of exonuclease I from E. coli. (Work of Rhett Kovall and Wendy Breyer in the Matthews laboratory).

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.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

The Bragg legacy: early days in macromolecular crystallography.
Matthews BW
Acta crystallographica. Section A, Foundations of crystallography 2013
Proteins under pressure.
Matthews BW
Proceedings of the National Academy of Sciences of the United States of America 2012
Stoichiometry versus hydrophobicity in protein folding.
Matthews BW
Journal of biomolecular structure & dynamics 2011
Peripatetic proteins.
Matthews BW
Protein science : a publication of the Protein Society 2010
Lessons from the lysozyme of phage T4.
Baase WA, Liu L, Tronrud DE, Matthews BW
Protein science : a publication of the Protein Society 2010
Boron mimetics: 1,2-dihydro-1,2-azaborines bind inside a nonpolar cavity of T4 lysozyme.
Liu L, Marwitz AJ, Matthews BW, Liu SY
Angewandte Chemie (International ed. in English) 2009
Direct and indirect roles of His-418 in metal binding and in the activity of beta-galactosidase (E. coli).
Juers DH, Rob B, Dugdale ML, Rahimzadeh N, Giang C, Lee M, Matthews BW, Huber RE
Protein science : a publication of the Protein Society 2009
Racemic crystallography--easy crystals and easy structures: what's not to like?
Matthews BW
Protein science : a publication of the Protein Society 2009
Contributions of all 20 amino acids at site 96 to the stability and structure of T4 lysozyme.
Mooers BH, Baase WA, Wray JW, Matthews BW
Protein science : a publication of the Protein Society 2009
Evaluation at atomic resolution of the role of strain in destabilizing the temperature-sensitive T4 lysozyme mutant Arg 96 --> His.
Mooers BH, Tronrud DE, Matthews BW
Protein science : a publication of the Protein Society 2009
A review about nothing: are apolar cavities in proteins really empty?
Matthews BW, Liu L
Protein science : a publication of the Protein Society 2009
Sorting the chaff from the wheat at the PDB.
Tronrud DE, Matthews BW
Protein science : a publication of the Protein Society 2009
Use of experimental crystallographic phases to examine the hydration of polar and nonpolar cavities in T4 lysozyme.
Liu L, Quillin ML, Matthews BW
Proceedings of the National Academy of Sciences of the United States of America 2008