John W. Keller Professor of Chemistry and Biochemistry University of Alaska Fairbanks

Interests Chemistry a-methyl amino acids, and related enzymes and gene regulators, such as the dialkylglycine decarboxylase and DgdR gene regulator. Other LysR-type gene regulators. Computational chemistry and biochemistry.

Current Research

Structure and Function of Burkholderia cepacia 2,2-dialkylglycine decarboxylase (E.C. 4.1.1.64). This remarkable enzyme is a pyridoxal 5'-phosphate dependent aminotransferase that catalyzes sequential decarboxylation of simple 2-methyl-substituted amino acids, followed by amino group transfer to small alpha-keto acids such as pyruvate or alpha-ketobutyrate. Currently we are investigating several aspects of this enzyme including (1)  structure determination and kinetics of inactivation by optically active 2-trifluoromethylalanine mechanism based inhibitors, and (2) studies of the role of quaternary structure in regulation and catalysis.

Structure and Function of the LysR-type gene regulators. The DgdR protein is encoded by a gene just upstream of and divergent from the dgdA gene that encodes the 2,2-dialkylglycine decarboxylase. This protein is a member of the large LysR family of transcription regulators. DgdR seems to be similar to other LysR proteins in causing a bend in DNA near the dgdA promoter. We are investigating the detailed structure and dynamics of the bent complex. Also we are cloning and expressing various LysR-type proteins that will be amenable to structural studies, such as LysR-type gene regulators in hyper- and hypothermophilic prokaryotes. 

Application of Functional Genomics to Soil Amino Acid Metabolism.  We are currently cloning dgd genes from soil isolates that utilize 2-methylalanine as a sole nitrogen source, and from well known species containing orthologues of the B. cepacia dgd genes. About 20 different species that seem to use AIB have have been identified by16 rRNA gene sequencing. Do all these organisms contain dgd-type genes? If so, how similar are the encoded DgdA and DgdR proteins to known proteins, and can we use the sequence variations to help build 3D models of these proteins?

Computational Chemistry. We have undertaken several computational studies based on student projects in undergraduate lecture and lab classes. These take advantage of UA's excellent facilities for computational chemistry, including parallel version of Gaussian03 installed on a 5-teraflop IBM P-69x supercomputer at the Arctic Region Supercomputing Center, and a statewide multi-user license for HyperChem. One ongoing project concerns the properties of a carboxylic acid "bimolecule", a complex of formic acid and trifluoroacetic acid whose gas-phase vibrational spectrum has been obtained in our lab. These complexes contain molecules doubly-hydrogen-bonded similar to the cyclic hydrogen bonds found in the A-T DNA base pair. One question that is needs to be answered is, Do the hydrogens in this complex exchange between the acids faster or slower compared to symmetric carboxylic acid complexes? Since hydrogen transfer in this complex must be accompanied by rotation of the CF₃ group, does this make hydrogen transfer slower or faster? In general, non-covalent interactions may play a significant role in determining the chemical properties of molecules in the atmosphere. Quantitative estimates of the energy content, vibrational and rotational spectra, and geometry of the ground- and electronic exited states of such complexes is now possible using high-level computational chemistry methods.

Click here for a list of: relevant publications,

Student projects:

Teaching Spring 2008:

Organic Chemistry Lab, Chem 324
Chemistry Seminar, Chem 481/482/692
Enzymology and Bioorganic Chemistry Chem 621

Weekly Schedule

Molecular graphics related to current research

Here are 2 molecular images that illustrate issues under active research in our group. You will be able to see these molecules only if you have the Chime plug-in installed. Right-click on the molecule to bring up an options menu: Shift-click and drag with the left mouse button to zoom the image. See the MDL Chime Web page for more information, and to obtain the plug-in.

CysB dimer x-ray structure, a prototype for DgdR and other LysR-type gene regulators.
Dialkylglycine decarboxylase active site.

Address

Department of Chemistry and Biochemistry
University of Alaska Fairbanks
900 Yukon Drive
Fairbanks, AK 99775-6160

Telephone: 907-474-6042
Fax: 907-474-5640
Email: ffjwk@uaf.edu

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