Ref. Code
US-CH-2481
Title
Enzyme dynamics of novel antibiotic targets
Last name
Boehr
First name
David
Name of University, Organisation
Pennsylvania State University
Name of Institute / Department
Department of Chemistry
Addition to address
Street
104 Chemistry Building
Postal code
16802
Town
University Park
State/Province
Pennsylvania
Country
US
Telephone
1-814-863-8605
Fax
E-mail Address
ddb12@psu.edu
Website
http://research.chem.psu.edu/ddbgroup/Boehr_Website/Welcome.html
Position currently holding
Assistant Professor
Field of Study
Chemistry - CH
Specialisation
Biochemistry
Key words
biochemistry, biophysics, molecular biology, protein, enzyme, catalysis, kinetics, thermodynamics, NMR, nuclear magnetic re
Requirements
basic chemistry/biology lab skills, including weighing, volume measurements, pipetting
some knowledge of protein structu
Subject of doctoral thesis
Supervisor of doctoral thesis
Email of Supervisor
-
Description of project and work placement, experimental techniques and possible tasks to be assigned to the research
Our lab is interested in the role of internal protein fluctuations to enzyme catalysis and regulation. The student will work clos
Upload project description
5950-343-daad-rise-summary-igps-2012.pdf
Working language
en
Suggested starting date (yyyy-monthname-dd)
2013-June-01
Duration of internship
10 weeks
Can supervisor assist intern in finding housing?
yes
Estimated costs of housing?
$500-1000 US / month
David D. Boehr, Ph.D.
Assistant Professor
The Pennsylvania State University
Department of Chemistry
240 Chemistry Building
University Park, PA 16802
Office: (814) 863-8605
Fax: (814) 865-3314
E-mail: ddb12@psu.edu
DAAD-RISE Project Description
Enzyme catalysis is an inherently dynamic process; distances between substrate atoms change
over time as chemical bonds are broken or formed. Enzymes themselves are dynamic macromolecules as
they experience fluctuations over many amplitudes and timescales, from local backbone fluctuations
occurring over picoseconds to nanoseconds to global, concerted conformational changes occurring over
microseconds to seconds. It has been proposed that the fluctuations experienced by enzymes may aid
directly in enzyme catalysis. Indeed, dynamic measurements suggest that enzymes experience
fluctuations over the same timescale as enzyme catalysis. However, while a correlation between enzyme
kinetics and the kinetics of protein motion is consistent with a role for protein dynamics in enzyme
function, it does not establish whether fluctuations observed in the enzyme (e.g. loop motion) are coupled
to the motions of reacting substrate atoms (e.g. closing of the distance between carbon atoms to facilitate
carbon-carbon bond formation). Studies that monitor both enzyme and substrate conformational dynamics
are necessary for a basic understanding of enzyme catalysis, and will provide insight into the role(s)
protein dynamics play in enzyme catalysis.
As part of these larger project goals, the DAAD-RISE participant will work closely with an
assigned graduate student to study the effects of amino acid mutations on the structure, function and
dynamics of important enzyme(s) in the tryptophan biosynthetic pathway. For example, the enzyme,
indole-3-glycerol phosphate synthase (IGPS), has been shown to be critical to bacterial survival and has
been suggested to be a target for novel antimicrobial compounds. The participant will learn basic
biochemical and molecular biology techniques required by a wide range of research. More specifically,
the participant will purify site-directed mutant proteins and characterize them in terms of enzyme activity
through enzyme assays, and protein stability through calorimetric approaches. The participant may also
be involved in characterizing structural dynamics through the use of state-of-the-art nuclear magnetic
resonance (NMR) techniques.
The Pennsylvania State University is located in picturesque State College, Pennsylvania that is
within driving distance to many major American cities including Pittsburgh (~3 hours), Philadelphia (~3
hours), Baltimore (~3-4 hours), Washington D.C. (~3-4 hours) and New York City (~4 hours). Our
International Office will work closely with applicants in visa application and finding temporary
accommodations.
Contact:
Dr. David D. Boehr
e-mail: ddb12@psu.edu
office: 001-814-863-8605