Institute of Molecular Biology

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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

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

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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 Crystallogr A 2013 Jan;69(Pt 1):34-6
Proteins under pressure.
Matthews BW
Proc Natl Acad Sci U S A 2012 May 1;109(18):6792-3
Stoichiometry versus hydrophobicity in protein folding.
Matthews BW
J Biomol Struct Dyn 2011 Feb;28(4):589-91; discussion 669-674
Lessons from the lysozyme of phage T4.
Baase WA, Liu L, Tronrud DE, Matthews BW
Protein Sci 2010 Apr;19(4):631-41
Peripatetic proteins.
Matthews BW
Protein Sci 2010 Jul;19(7):1279-80
Sorting the chaff from the wheat at the PDB.
Tronrud DE, Matthews BW
Protein Sci 2009 Jan;18(1):2-5
A review about nothing: are apolar cavities in proteins really empty?
Matthews BW, Liu L
Protein Sci 2009 Mar;18(3):494-502
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 Sci 2009 May;18(5):871-80
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 Sci 2009 Jun;18(6):1281-92
Use of stabilizing mutations to engineer a charged group within a ligand-binding hydrophobic cavity in T4 lysozyme.
Liu L, Baase WA, Michael MM, Matthews BW
Biochemistry 2009 Sep 22;48(37):8842-51
Boron mimetics: 1,2-dihydro-1,2-azaborines bind inside a nonpolar cavity of T4 lysozyme.
Liu L, Marwitz AJ, Matthews BW, Liu SY
Angew Chem Int Ed Engl 2009;48(37):6817-9
Structural basis for the unusual specificity of Escherichia coli aminopeptidase N.
Addlagatta A, Gay L, Matthews BW
Biochemistry 2008 May 13;47(19):5303-11
Use of experimental crystallographic phases to examine the hydration of polar and nonpolar cavities in T4 lysozyme.
Liu L, Quillin ML, Matthews BW
Proc Natl Acad Sci U S A 2008 Sep 23;105(38):14406-11
Five retracted structure reports: inverted or incorrect?
Matthews BW
Protein Sci 2007 Jun;16(6):1013-6
Protein Structure Initiative: getting into gear.
Matthews BW
Nat Struct Mol Biol 2007 Jun;14(6):459-60
Changes to crystals of Escherichia coli beta-galactosidase during room-temperature/low-temperature cycling and their relation to cryo-annealing.
Juers DH, Lovelace J, Bellamy HD, Snell EH, Matthews BW, Borgstahl GE
Acta Crystallogr D Biol Crystallogr 2007 Nov;63(Pt 11):1139-53
Co-repressor induced order and biotin repressor dimerization: a case for divergent followed by convergent evolution.
Wood ZA, Weaver LH, Brown PH, Beckett D, Matthews BW
J Mol Biol 2006 Mar 24;357(2):509-23
Sequential reorganization of beta-sheet topology by insertion of a single strand.
Sagermann M, Baase WA, Matthews BW
Protein Sci 2006 May;15(5):1085-92
Guanidinium derivatives bind preferentially and trigger long-distance conformational changes in an engineered T4 lysozyme.
Yousef MS, Bischoff N, Dyer CM, Baase WA, Matthews BW
Protein Sci 2006 Apr;15(4):853-61
Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site.
Addlagatta A, Gay L, Matthews BW
Proc Natl Acad Sci U S A 2006 Sep 5;103(36):13339-44
Determination of solvent content in cavities in IL-1beta using experimentally phased electron density.
Quillin ML, Wingfield PT, Matthews BW
Proc Natl Acad Sci U S A 2006 Dec 26;103(52):19749-53
The structure of E. coli beta-galactosidase.
Matthews BW
C R Biol 2005 Jun;328(6):549-56
Structural basis for the functional differences between type I and type II human methionine aminopeptidases.
Addlagatta A, Hu X, Liu JO, Matthews BW
Biochemistry 2005 Nov 15;44(45):14741-9
Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin.
Juers DH, Kim J, Matthews BW, Sieburth SM
Biochemistry 2005 Dec 20;44(50):16524-8