Place: B2 Library
Time: 11.00 am
Day:  Oct 23, Tuesday
Speaker: Lakshminarayan M. Iyer

Origins, functional diversity, and convergences in protein-conjugating enzymes

The E1-like superfamily is central to ubiquitin (Ub) conjugation, biosynthesis of cysteine, thiamine, and MoCo, and several secondary metabolites. 
I shall present a synthetic overview of the functional diversity and evolutionary history of this class of enzymes. Some major highlights that will 
be described include: 1) The relationship of the E1-like superfamily to the  NAD(P)/FAD-dependent dehydrogenases and
S-AdoMet- dependent methylases of the Rossmannoid fold and its implication for the evolution of phospho- and sulfo-transfer activities.
2) The striking sequence, structure, and functional diversity within these enzymes that point to their participation in several uncharacterized bacterial 
secondary metabolism pathways, novel cysteine biosynthesis systems, metal sulfur cluster assembly and tRNA thiobase biosynthesis. 3) The domain fusions
 of the E1-like proteins that suggest a generalized model for the linking of E1 catalyzed adenylation/thiolation with further downstream reactions. 

Recently, pupylation, a system analogous to ubiqutination was discovered in Mycobacteria where a protein ligand, Pup is transferred to the epsilon amino 
groups of lysine residues. Proteins targeted by this mechanism are subsequently degraded by the archaeal-type proteasome. I shall describe the uncovering
 of the Pup-ligase and its unification to the glutamine synthetase superfamily that provides a simple biochemical mechanism for this process. Pupylation 
represents a remarkable case of convergent evolution where, as in Ub conjugation, a protein conjugation system evolved from cofactor and amino acid 
biosynthesis pathways for protein degradation from entirely unrelated components.

Lakshminarayan Iyer
http://www.ncbi.nlm.nih.gov/CBBresearch/Lakshmin/