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The evolution and structural anatomy of small molecule metabolism pathways in Escherichia coli .

The evolution and structural anatomy of small molecule metabolism pathways in Escherichia coli. Of Pathways and Proteins Stuart Rison and Sarah Teichmann. Questions. How are homologous proteins (enzymes) distributed in E. coli metabolism?

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The evolution and structural anatomy of small molecule metabolism pathways in Escherichia coli .

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  1. The evolution and structural anatomy of small molecule metabolism pathways in Escherichia coli. Of Pathways and Proteins Stuart Rison and Sarah Teichmann

  2. Questions • How are homologous proteins (enzymes) distributed in E. coli metabolism? • How does this distribution fit with theories of pathway evolution?

  3. Pathway evolution • Norman Horowitz, 1945: ‘On the evolution of biochemical syntheses’, Proc. Nat. Acc. Sci. 31:153-157. “Retrograde evolution” • Roy Jensen, 1976: ‘Enzyme recruitment in evolution of new function’, Ann. Rev. Microbiol 30:409-425. “Patchwork evolution”

  4. [ ] [ ] [ ] Retrograde evolution

  5. Jensen, 1976: Substrate ambiguity • ‘Original pool’ of unregulated and enzymatically versatile proteins • Enzymes recruited from the pool • Ad hoc pathways • Gene duplication and specialisation leads to regulated, specific and efficient pathways

  6. Patchwork evolution

  7. An extensively studied model organism Complete genome available Most Small Molecule Metabolism pathways well known and empirically characterised A manageable size Good associated databases Why E. coli?

  8. Strategy • Identify all SMM proteins and the pathway(s) in which they belong • Detect homologous proteins by structure or sequence • Combine these data to analyse homologous protein distribution in SMM

  9. SCOP Methods E. coli IMPALA EcoCyc HMM Y-BLAST + = Structural Anatomy Y-BLAST (>75aa) Evolutionary Relationships Pathways Proteins

  10. Domain assignments 566 SMM proteins 124 unassigned proteins 442 proteins assigned to 1+ families (78%) 169 PDB-D families 31 ‘sequence’ domain families 200 domain families

  11. Glycogen Catabolism Domains Glycosyltransferases Chemistry and close substrate Chemistry and substrate a-amylase, C-term Internal duplication Isozymes b-glucosyltransferase Phosphoglucomutase glycogen phosphorylase a-amylase, 3.2.1.1 a-amylase, 3.2.1.1 malS amyA glgP phosphoglucomutase, 5.4.2.2 malodextrin phosphorylase malP pgm malodextrin glucosidase amylomaltase, 2.4.1.25 malZ malQ

  12. Duplications Across Pathways • 110 out of 200 families occur in more than one pathway • Can exhibit conservation of chemistry, shared cofactor or minor substrate similarity • 36 families have close conservation of EC number (Chemistry conserved) • 74 families conserve 1 or no EC number; 11 are cofactor-binding families (cofactor, minor substrate)

  13. Duplications within and across Pathways • 710 domains in 200 families • 510 domains have arisen by duplication • 232 duplications within pathways to 278 duplications across pathways (Assumption: duplication within pathways wherever possible.)

  14. Type of conservation

  15. Conclusion: Structural Anatomy • 710 domains in 442 proteins of the 566 proteins in E. coli SMM pathways • 200 families (3.5 members/family) • Most sizeable families are distributed in several pathways

  16. Conclusion: Recruitment and Conservation • Duplications have taken place between and within pathways to roughly the same degree • Duplications occur within most longer pathways: • Isozymes, internal duplications and co-factor binding most common • Chemistry common • Conservation of substrate binding with modified chemistry is rare

  17. Conclusions: Pathway evolution • Data support a “patchwork evolution” model • Little evidence of “retrograde evolution”

  18. Conclusions: hum… • Recruitment, duplication and evolution of enzymes are constantly taking place so we are always observing a dynamic system • Likely to be other evolutionary mechanisms and combinations thereof

  19. Future • Identification and analysis of novel pathway duplication events • Focus on order in pathways: • Stepwise analysis • Doublet/triplet analysis • Analysis domain combination in SMM

  20. Acknowledgements • Sarah A. Teichmann, Dept. Biochemistry, University College London • Janet M. Thornton, David Lee, Dept. Crystallography, Birkbeck College and Dept. Biochemistry, University College London • Monica Riley, Alida Pelegrini-Toole, Marine Biology Laboratory, Woods Hole, USA • Cyrus Chothia, Julian Gough, MRC Laboratory of Molecular Biology, Cambridge, UK

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