James D. Moody
Office: C206 BNSN
Office Phone: 801-422-6272
Lab Room: C288 BNSN
University of Washington, Seattle, WA Doctor of Philosophy, August 2014
Dissertation: Computational and experimental engineering of novel binding proteins targeting cancer and epigenetic signaling pathways
Honors: National Science Foundation Graduate Research Fellowship, honorable mention, 2010 and 2011
Brigham Young University, Provo, UT Bachelor of Science, April 2007
Major: Physiology and Developmental Biology
Honors: Brigham Young Scholarship, 2005. W.D. Snow Scholarship, 2006. Office of Research and Creative Activities grant recipient, 2007. Graduated magna cumlaude, 2007.
Glendale Community College, Glendale, AZ Associate of Science, May 2005
Major: General Studies
Honors: Full tuition scholarship, 2000. Half tuition scholarship, 2004.
The Moody Lab is currently working to develop generalizable protein engineering-based methods to facilitate protein structure determination by X-ray crystallography.
Moody Lab Approach
X-ray crystallography allows researchers to determine the structure of proteins at the atomic level, helping science to understand how protein dysfunction causes disease, develop new treatments, and engineer new protein-based tools. Unfortunately, X-ray crystallography is only useful for those proteins that can be induced to form ordered crystals; about 20-30% of all known proteins.1 Recently the Moody Lab engineered a variant of pyruvate formate-lyase activating enzyme (PFL-AE-H), a radical SAM enzyme, for facile crystallization. Researchers observed that while the engineered PFL-AE variant formed at least 4 different crystal packing arrangements (lattices), all of these shared a conserved screw axis. Screw axes can be thought of as ordered fibers composed of stacked copies of the protein. Since this screw axis is common among 4 different crystal lattices, Moody researchers propose that it forms first during crystal nucleation and serves to dictate the packing arrangement of the rest of the crystal. Currently the Moody Lab is investigating fusing proteins of interest to engineered screw axis fibers to pre-order them and nucleate crystal formation. It is the Moody Lab's hope that new protein crystallization methods like this one will enable structure determination of a much greater percentage of known proteins and greatly accelerate scientific discovery and disease treatment.
PFL-AE-H in its crystal lattice 4 distinct PFL-AE-H lattices share a screw axis
Synthetic screw axes could pre-order proteins of interest
In the Moody lab students will learn computational protein modeling and design, molecular biology techniques, protein biochemistry, and macromolecular X-ray crystallography. If students are interested, Dr. Moody would love to talk with them. The Moody Lab welcomes dedicated, hard-working students with all levels of experience, including beginning students. Be prepared to dedicate at least 10 hours per week to the research to make meaningful progress.
To learn more about radical SAM enzymes and some of the first proteins that the Moody Lab aims to crystallize, keep reading!
Radical SAM enzymes create highly reactive organic radicals and use them to accomplish a huge variety of high-energy chemical transformations in substrate molecules, nucleic acids, and other proteins.2
Radical SAM activation mechanism
Right now the Moody Lab is studying the interactions between a radical SAM enzyme, glycerol dehydratase activating enzyme (GD-AE), and its substrate, B12-independent glycerol dehydratase (GD).2 Moody researchers have modeled the complex and are working to determine its atomic structure using chemical crosslinking, mass spectrometry, protein engineering, and crystallography. This will help Moody Lab students understand the role and mechanism of the unusual ferredoxin domain of GD-AE and the mechanism by which the GD substrate peptide receives the radical modification and is re-inserted into the GD active site.
Homology model of GD-AE bound to GD
Using the same approaches, the Moody Lab Group is also studying the interactions between the FeFe-hydrogenase maturases HydE, HydF, and HydG. Structural characterization of complexes of these enzymes will provide clues to the identity of the elusive HydE substrate and the mechanism by which these maturases assemble the complex 2-iron subcluster of FeFe-hydrogenase.2
Structures of Hydrogenase Maturases
- Lin HL, James I, Hyer CD, Haderlie CT, Zackrison MJ, Bateman TM, Berg M, Park JS, Daley
SA, Zuniga Pina NR, Tseng YJ, Moody JD, Price JC. Quantifying In Situ Structural
Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability
Assay. J Proteome Res. 2022 Dec 2;21(12):2920-2935.
- Nawarathnage S, Soleimani S, Mathis MH, Bezzant BD, Ramírez DT, Gajjar P, Bunn DR,
Stewart C, Smith T, Pedroza Romo MJ, Brown S, Doukov T, Moody JD. Crystals of
TELSAM-target protein fusions that exhibit minimal crystal contacts and lack direct inter-
TELSAM contacts. Open Biol. 2022 Mar;12(3):210271.
- Walls WG, Moody JD, McDaniel EC, Villanueva M, Shepard EM, Broderick WE, Broderick JB.
The B12-independent glycerol dehydratase activating enzyme from Clostridium butyricum
cleaves SAM to produce 5´-deoxyadenosine and not 5´-deoxy-5´-(methylthio)adenosine.
Journal of Inorganic Biochemistry. 2022 Feb;227:111662.
- Chan TY, Egbert CM, Maxson JE, Siddiqui A, Larsen LJ, Kohler K, Balasooriya ER, Pennington
KL, Tsang TM, Frey M, Soderblom EJ, Geng H, Müschen M, Forostyan TV, Free S,
Mercenne G, Banks CJ, Valdoz J, Whatcott CJ, Foulks JM, Bearss DJ, O'Hare T, Huang
DCS, Christensen KA, Moody J, Warner SL, Tyner JW, Andersen JL. TNK1 is a ubiquitin-
binding and 14-3-3-regulated kinase that can be targeted to block tumor growth. Nat
Commun. 2021 Sep 9;12(1):5337.
- Coates TL, Young N, Jarrett AJ, Morris CJ, Moody JD, Della Corte D, Current computational
methods for enzyme design. Modern Physics Letters B. 2021;33(0):2150155-1–30.
Click here to view full Curriculum Vitae.
- Dale GE, Oefner C, D'Arcy A. The protein as a variable in protein crystallization. J Struct Biol. 2003 Apr;142(1):88-97.
- Broderick JB, Duffus BR, Duschene KS, Shepard EM. Radical S-adenosylmethionine enzymes. Chem Rev. 2014 Apr 23;114(8):4229-317.