Peter Moody

Short Biography

Peter Moody joined the University of Leicester as Professor of Structural Biology in 1995 and currently leads a research group at the Department of Molecular and Cell Biology. The group's work focuses on exploring the structures and mechanisms of redox and other enzymes, involving techniques such as X-ray crystallography to determine overall structures and neutron crystallography to pinpoint the positions of hydrogen atoms.

Peter Moody obtained his PhD in Physics at Imperial College London, where he studied the mechanism of the glycolytic enzyme Glyceraldehyde 3-Phosphate Dehydrogenase. Following his PhD, he held positions at Harvard, Imperial College, and York, where he continued to use protein crystallography to investigate enzyme mechanisms.

AMBER postdoctoral fellowship subject (second call)

Unravelling the mechanism by which haem modulates the activity of transcription factors

It is becoming clear that the cell biology of haem is wider than its role as a prosthetic group in housekeeping proteins[11]. Haem might not always be inextricably linked to a host, or pivotal to a protein’s functional activity. One example is its ability to modulate the behaviour of transcription factors, such as those that generate the internal-timekeeping system of the mammalian-molecular clock. This type of haem-protein interaction must be transient and reversible, in contrast to the tight binding of a prosthetic group. Whilst certain sequences of amino acids have been implicated as haem-recognition motifs, there is still uncertainty about how haem binds to transcription factors. The reversible nature of the interaction suggests that the binding sites must be altogether different to the binding pockets in haemoproteins. The binding of haem to the transcription factor can be expected to induce a significant conformational change which might prevent its association to DNA (or cause an existing DNA-protein complex to dissociate). In addition, as a consequence of the toxicity of free molecules of haem, we must assume that transcription factors acquire haem via ligand-substitution reactions[3] from a chaperone; a protein that is suspected to moonlight as a haem chaperone is GAPDH[2]. This project will investigate transient haem-protein interactions by utilizing structural biology to reveal the ligand-binding site, and different biophysical approaches to reveal the conformational dynamics of the transition between the apo and holo protein, along with mechanistic detail of haem-substitution reactions from an exemplar chaperone, GAPDH to an acceptor protein. 

 Project leadership team: Hanna Kwon (University of Leicester), Andrew Hudson (University of Leicester), Peter Moody University of Leicester). Co-investigator: Kajsa Sigfridsson Clauss (MAX IV laboratory). Collaborators: Charalambos Kyriacou (University of Leicester), Ezio Rosato (University of Leicester), Emma Raven (University of Bristol)

1. Basran, J., et al., Binding of l-kynurenine to X. campestris tryptophan 2,3-dioxygenase. J Inorg Biochem, 2021. 225: p. 111604.

2. Biswas, P., Y. Dai, and D.J. Stuehr, Indoleamine dioxygenase and tryptophan dioxygenase activities are regulated through GAPDH- and Hsp90-dependent control of their heme levels. Free Radic Biol Med, 2022. 180: p. 179-190.

3. Leung, G.C., et al., Unravelling the mechanisms controlling heme supply and demand. Proc Natl Acad Sci U S A, 2021. 118(22).

4. Kwon, H., et al., XFEL Crystal Structures of Peroxidase Compound II. Angew Chem Int Ed Engl, 2021. 60(26): p. 14578-14585.

5. Tourigny, D.S., et al., Expression, purification, crystallization and preliminary X-ray analysis of wild-type and of an active-site mutant of glyceraldehyde-3-phosphate dehydrogenase from Campylobacter jejuni. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2011. 67(Pt 1): p. 72-5.

6. Yan, J.J., et al., Resonant inelastic X-ray scattering determination of the electronic structure of oxyhemoglobin and its model complex. Proc Natl Acad Sci U S A, 2019. 116(8): p. 2854-2859.

7. Baker, M.L., et al., K- and L-edge X-ray Absorption Spectroscopy (XAS) and Resonant Inelastic X-ray Scattering (RIXS) Determination of Differential Orbital Covalency (DOC) of Transition Metal Sites. Coord Chem Rev, 2017. 345: p. 182-208.

8. Wilson, S.A., et al., X-ray absorption spectroscopic investigation of the electronic structure differences in solution and crystalline oxyhemoglobin. Proc Natl Acad Sci U S A, 2013. 110(41): p. 16333-8.

9. Kuhl, T., et al., Analysis of Fe(III) heme binding to cysteine-containing heme-regulatory motifs in proteins. ACS Chem Biol, 2013. 8(8): p. 1785-93.

10. Freeman, S.L., et al., Heme binding to human CLOCK affects interactions with the E-box. Proc Natl Acad Sci U S A, 2019. 116(40): p. 19911-19916.

11. Shimizu, T., et al., Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres. Chem Soc Rev, 2019. 48(24): p. 5624-5657.

Location: Leicester, UK

Organisation: University of Leicester, The Department of Molecular and Cell Biology

Links

AMBER call in EURAXESS main call (starting point for application)

Guide for applicants

Peter Moody's Profile on the University of Leicester website

The Department of Molecular and Cell Biology, University of Leicester

Info about employment at the University of Leicester