Metabolism & Organelle Biogenesis

Group Site: 
Group Leader: 

Wyatt W. Yue 余偉賢

Group Info

Research Areas

Our Mission Statement

We explore how proteins and protein-protein interactions play a role in metabolism and organelle biogenesis

We seek to understand how genetic defects and protein malfunctions cause inborn errors of metabolism (IEM)

We work closely with clinicians and pathologists with the common goal of advancing IEM diagnosis, screening and treatment.

Our Research Activities

Structure determination, functional characterisation and chemical biology programs for metabolic enzymes and regulatory proteins are the objectives of our group, and will contribute to an increased understanding of metabolism and organelle biogenesis. Our research activities can be summarized below (click on each tablet for further details).

 

Structures

Inborn Errors of Metabolism Proteome

We have determined more than 150 novel human structures, spanning many areas of metabolism. 

A subset of them (~30) are linked with inborn errors of metabolism (click on name of the protein for structure info):

 

Group Members
Wyatt Yue
D. Sean Froese
Wasim Kiyani
Publications

A full, up-to-date publication list of the MOB lab can be found here.

1. Pilka E, Kochan G, Oppermann U, Yue WW* (2012) Crystal structure of the secretory isozyme of mammalian carbonic anhydrases CA VI: Implications for biological assembly and inhibitor development. Biochem Biophys Res Comm in press

2. Chaikuad A, Froese DS, Berridge G, von Delft F, Oppermann U, Yue WW* (2011) Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis. PNAS 108(52):21028-33

3. Hillringhaus L, Yue WW, Rose NR, Ng SS, Gileadi C, Loenarz C, Bello SH, Bray JE, Schofield CJ, Oppermann U (2011) Structural and Evolutionary Basis for the Dual Substrate Selectivity of Human KDM4 Histone Demethylase Family. J Biol Chem. 286(48):41616-25.3. 

4. Lee WH, Yue WW, Raush E, Totrov M, Abagyan R, Oppermann U, Marsden BD (2011) Interactive JIMD articles using the iSee concept: turning a new page on structural biology data. J Inherit Metab Dis. 34(3):565-7

5. Picaud S, Kavanagh K, Yue WW, Muller S, Gileadi O, Sacchettini J, and Oppermann U (2011) Structural Basis of fumarate hydratase deficiency. J Inherit Metab Dis, 34(3):671-6

6. Yue WW*, Oppermann U (2011) High-throughput structural biology of metabolic enzymes and its impact on human diseases. J Inherit Metab Dis, 34(3):575-81

7. Chaikuad A, Shafqat N, Al-Mokhtar R, Cameron G, Clark T, Brady RL, Oppermann U, Frayne J, Yue WW* (2011) Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS. Biochemical J, 435:401-409.

8. Froese DS, Kochan G, Muniz J et al, Gravel RA, Oppermann U, Yue WW* (2010) Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. J Biol Chem, 285:38204-38213.

9. Healy S, McDonald MK, Wu X, Yue WW, Kochan G, Oppermann U, Gravel RA (2010) Structural impact of human and Escherichia coli biotin carboxyl carrier proteins on biotin attachment. Biochemistry 49:4687-4694

10. Shafqat N, Turnbull A, Zschocke J, Oppermann U, Yue WW* (2010) Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. J Mol Biol 398:497-506

11. Yue WW, Hozjan V, Ge W, Loenarz C, Cooper CD, Schofield CJ, Kavanagh KL, Oppermann U, McDonough MA (2010) Crystal structure of the PHF8 jumonji domain, an Nε-methyl lysine demethylase. FEBS Lett 584:825-830

12. Kochan G, Pilka ES, von Delft F, Oppermann U, Yue WW* (2009) Structural snapshots of two-step catalytic pathway for human medium-chain acyl-coenzyme A synthetase. J Mol Biol 388:997-1008

13. Picaud S, Muniz JRC, Pilka ES, Kochan G, Oppermann U, Yue WW* (2009) Crystal structure of human carbonic anhydrase-related protein VIII reveals the basis for catalytic silencing. Proteins 76:507-511

14. Ng SS, Yue WW, Oppermann U, Klose RJ (2009) Dynamic protein methylation in chromatin biology. Cell Mol Life Sci 66:407-422

15. Hassler M, Singh S, Yue WW, Lucynski M, Lakbir R, Pearl LH, Mittnacht S (2007) Crystal structure of the retinoblastoma protein N domain provides insight into tumor suppression, ligand interaction, and holoprotein architecture. Mol Cell 28:371-385

16. Yue WW, Hassler M, Roe SM, Thompson-Vale V, Pearl LH (2007) Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase. EMBO J 26:4402-4412

17. Schalk IJ, Yue WW, Buchanan SK (2004) Recognition of iron-free siderophores by TonB-dependent iron transporters. Mol Microbiol 54:14-22

18. Yue WW, Grizot S, Buchanan SK (2003) Structural evidence for iron-free citrate and ferric citrate binding to the TonB-dependent outer membrane transporter FecA. J Mol Biol 332:353-6

Contact

wyatt [dot] yue[at]sgc [dot] ox [dot] ac [dot] uk (Dr Wyatt W. Yue)

SGC
University of Oxford
Old Campus Research Building
Roosevelt Drive
Headington
Oxford
OX3 7DQ
UK 

Tel: +44 (0)1865 617757