Leonard MuellerProfessor of Chemistry & ChairChemistry Dept lmueller@ucr.edu(951) 827-3565
NMR Crystallography: Linking Chemical Structure and Mechanism in Tryptophan Synthase
AWARD NUMBER
009169-002
FUND NUMBER
33370
STATUS
Closed
AWARD TYPE
3-Grant
|
AWARD EXECUTION DATE
7/26/2017
BEGIN DATE
8/1/2017
END DATE
7/31/2020
AWARD AMOUNT
$480,000
|
Sponsor Information
SPONSOR AWARD NUMBER
SPONSOR
SPONSOR TYPE
FUNCTION
Organized Research
PROGRAM NAME
Proposal Information
PROPOSAL NUMBER
17040527
PROPOSAL TYPE
New
ACTIVITY TYPE
Basic Research
PI Information
PI
Mueller, Leonard J
PI TITLE
Other
PI DEPTARTMENT
Chemistry
PI COLLEGE/SCHOOL
College of Nat & Agr Sciences
CO PIs
Fan, Li;
Project Information
ABSTRACT
This award is funded by the Chemistry Division's Chemistry of Life Processes Program. Professors Leonard Mueller and Li Fan from the University of California at Riverside bring together two of the tools of molecular imaging, nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, to describe an enzymatic reaction with atomic resolution (the ability to distinguish between atoms of a molecule and between molecules). Enzymes catalyze specific chemical reactions that impact nearly all life processes. Yet the details of how they do this remain elusive. In this study, the location of all atoms including hydrogens, the smallest of all atoms, are described as the reaction takes place. The result is a unique and detailed view into the reaction that shows how atoms move during the process. This new method is applied to one enzyme in particular, but the basic approach should be widely applicable to many enzymes. This research is carried out by graduate and undergraduate students at UC Riverside and by first-generation undergraduate students from neighboring Claremont colleges. The researchers share their results and experience at scientific conferences and in the local elementary and high schools.
This project develops of NMR-assisted crystallography, the synergistic combination of solid-state NMR spectroscopy, X-ray crystallography, and computational chemistry as an atomic-resolution probe of structure and dynamics in enzyme active sites. The goal is to understand the molecular basis for reaction specificity in the pyridoxal-5'-phosphate (PLP) dependent enzyme tryptophan synthase (TS). To accomplish this goal, Professors Mueller and Fan describe with atomic resolution, the transformation of substrates into product in the beta-subunit active site of TS. The location of all atoms is specified, including hydrogens, for multiple intermediates along the beta-reaction pathway. The combination of X-ray crystallography, solid-state NMR, and computational methodologies give chemically-rich detail that is not available when these methodologies are applied in isolation. Taken together, these techniques can provide consistent and testable models for structure and function in an enzyme active site: X-ray crystallography provides a coarse framework upon which models of the active site can be developed using computational chemistry. These models can be tested by comparisons of their first-principles predicted chemical shifts and the results of solid-state NMR spectroscopy experiments.(Abstract from NSF)
|