Brian Matthews
Brian Matthews

Professor of Physics
B.S., University of Adelaide;
Ph.D., University of Adelaide;
D.Sc., University of Adelaide
Member of: Institute of Molecular Biology
Office: Willamette Hall Room 376
Telephone: 541-346-2572
Fax: 541-346-5870

Lab: Willamette Hall Room 340
Telephone: 541-346-2570
Computer Room Telephone: 541-346-5874


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 labmatthews research

Model (left) showing the presumed mode by which lambda-exonuclease encloses DNA and processively hydrolyzes one of the two strands. The figure on the right 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.

Selected Publications

Quillin ML, Wingfield PT, Matthews BW. Abstract Determination of solvent content in cavities in IL-1beta using experimentally phased electron density. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19749-53.

Addlagatta A, Gay L, Matthews BW. Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site. Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13339-44.

Addlagatta A., Matthews, B. W. Structure of the angiogenesis inhibitor ovalicin bound to its noncognate target, human Type 1 methionine aminopeptidase. Protein Sci. 8,:1842-8. 2006 Aug;15

Hu, X., Addlagatta, A., Matthews, B.W. and Liu, J.O. (2006) Identification of pyridinylpyrimidines as inhibitors of human methionine aminopeptidases. Angewandte Chemie 45, 3772-3775.

Sagermann, M., Baase, W. A. and Matthews, B.W. (2006) Sequential reorganization of beta-sheet topology by insertion of a single strand. Protein Sci. 15, 1085-1092.

Yousef, M.S., Bischoff, N., Dyer, C.M., Baase, W.A. and Matthews, B.W. (2006) Guanidinium derivatives bind preferentially and trigger long-distance conformational changes in an engineered T4 lysozyme. Protein Sci. 15, 853-861.

Wood, Z.A., Weaver, L.H., Brown, P.H., Beckett, D. and Matthews, B. W. (2006) Co-repressor induced order and biotin repressor dimerization: A case for divergent followed by convergent evolution. J. Mol. Biol. 357, 509-523.

Mooers, B.H.M. and Matthews, B.W. (2006) Extension to 2268 atoms of direct methods in the ab initio determination of the unknown structure of bacteriophage P22 lysozyme. Acta Cryst. D62, 165-176.

Juers, D.H., Kim, J., Matthews, B.W. and Sieburth, S.McN. (2005) Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin. Biochemistry 44, 16524-16528.

Collins, M.D., Hummer, G., Quillin, M.L., Matthews, B.W. and Gruner, S.M. (2005) Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation. Proc. Natl. Acad. Sci. USA 102, 16668-16671.

Addlagatta, A., Hu, X., Liu, J.O. and Matthews, B.W. (2005) Structural basis for the functional differences between Type I and Type II human methionine aminopeptidases. Biochemistry 44, 14741-14749.

Desvaux, H., Dubois, L., Huber, G., Quillin, M.L., Berthault, P. and Matthews, B.W. (2005) Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy. J. Am. Chem. Soc. 127, 11676-11683.

Matthews, B.W. (2005) The structure of E. coli beta-galactosidase. C.R. Biologies 328, 549-556.

Addlagatta, A., Quillin, M.L., Omotoso, O., Liu, J.O. and Matthews, B.W. (2005) Identification of an SH3-binding motif in a new class of methionine aminopeptidases from Mycobacterium tuberculosis suggests a mode of interaction with the ribosome. Biochemistry 44, 7166-7174.

Yousef, M. and Matthews, B.W. (2005) Structural basis of Prospero-DNA interaction: Implications for transcription regulation in developing cells. Structure 13, 601-607.

Ostheimer G.J., H. Hadjivasiliou, D.P. Kloer, A. Barkan, and B.W. Matthews. (2005) Structural analysis of the group II intron splicing factor CRS2 yields insights into its protein and RNA interaction surfaces. J Mol Biol 345:51-68.

Mooers B.H., and B.W. Matthews (2004) Use of an ion-binding site to bypass the 1000-atom limit to structure determination by direct methods. Acta Crystallogr D Biol Crystallogr 60:1726-37.

Dyer C.M., M.L. Quillin, A. Campos, J. Lu, M.M. McEvoy, A.C. Hausrath, E.M. Westbrook, P. Matsumura, B.W. Matthews, and F.W. Dahlquist (2004) Structure of the constitutively active double mutant CheYD13K Y106W alone and in complex with a FliM peptide. J Mol Biol 342:1325-35.

He M.M., Z.A. Wood, W.A. Baase, H. Xiao, and B.W. Matthews (2004) Alanine-scanning mutagenesis of the beta-sheet region of phage T4 lysozyme suggests that tertiary context has a dominant effect on beta-sheet formation. Protein Sci 13:2716-24.

Yousef M.S., W.A. Baase, and B.W. Matthews (2004) Use of sequence duplication to engineer a ligand-triggered, long-distance molecular switch in T4 lysozyme. PNAS 101:11583-6.

Kingston R.L., D.J. Hamel, L.S. Gay, F.W. Dahlquist, and B.W. Matthews (2004) Structural basis for the attachment of a paramyxoviral polymerase to its template. PNAS 101:8301-6.

Wei B.Q., L.H. Weaver, A.M. Ferrari, B.W. Matthews, and B.K. Shoichet (2004) Testing a Flexible-receptor Docking Algorithm in a Model Binding Site. J Mol Biol 337:1161-82.

Juers D.H. and B.W. Matthews (2004) The role of solvent transport in cryo-annealing of macromolecular crystals. Acta Crystallogr D Biol Crystallogr 60:412-21.

Sagermann M., W.A. Baase, B.H. Mooers, L. Gay, and B.W. Matthews (2004) Relocation or duplication of the helix a sequence of T4 lysozyme causes only modest changes in structure but can increase or decrease the rate of folding. Biochemistry 43:1296-301.

Carmel A.B. and B.W. Matthews (2004) Crystal structure of the BstDEAD N-terminal domain: a novel DEAD protein from Bacillus stearothermophilus. RNA 10:66-74.

Department of Physics | Department of Chemistry | Department of Biology | UO Life Sciences | University of Oregon