Structural highlights
Publication Abstract from PubMedgamma-Glutamyl transpeptidases (gamma-GTs) are members of N-terminal nucleophile hydrolase superfamily. They are synthetized as single-chain precursors, which are then cleaved to form mature enzymes. Basic aspects of autocatalytic processing of these pro-enzymes are still unknown. Here we describe the X-ray structure of the precursor mimic of Bacillus licheniformis gamma-GT (BlGT), obtained by mutating catalytically important threonine to alanine (T399A-BlGT), and report results of autoprocessing of mutants of His401, Thr415, Thr417, Glu419 and Arg571. Data suggest that Thr417 is in a competent position to activate the catalytic threonine (Thr399) for nucleophilic attack of the scissile peptide bond and that Thr415 plays a major role in assisting the process. On the basis of these new structural results, a possible mechanism of autoprocessing is proposed. This mechanism, which guesses the existence of a six-membered transition state involving one carbonyl and two hydroxyl groups, is in agreement with all the available experimental data collected on gamma-GTs from different species and with our new Ala-scanning mutagenesis data. The maturation mechanism of gamma-glutamyl transpeptidases: Insights from the crystal structure of a precursor mimic of the enzyme from Bacillus licheniformis and from site-directed mutagenesis studies.,Pica A, Chi MC, Chen YY, d'Ischia M, Lin LL, Merlino A Biochim Biophys Acta. 2015 Oct 30. pii: S1570-9639(15)00268-X. doi:, 10.1016/j.bbapap.2015.10.006. PMID:26536828[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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