4lcq

Publication Abstract from PubMed

Lysine carbamylation, a post-translational modification, facilitates metal coordination for specific enzymatic activities. We have determined structures of the vertebrate dihydropyrimidinase from Tetraodon nigroviridis (TnDhp) in various states: the apo enzyme as well as two forms of the holo enzyme with one and two metals at the catalytic site. The essential active-site structural requirements have been identified with possible existence of four metal-mediated stages of lysine carbamylation. Only one metal is sufficient for stabilizing lysine carbamylation; however, the post-translational lysine carbamylation facilitates additional metal coordination for the regulation of specific enzymatic activities through controlling the conformations of two dynamic loops, Ala69-Arg74 and Met158-Met165, located in the tunnel for the substrate entrance. The substrate/product tunnel is in the open form in the apo-TnDhp, in the intermediate state in the mono-metal TnDhp, and in the close form in the di-metal TnDhp structure, respectively. Structural comparison also suggests that the C-terminal tail plays a role in the enzymatic function through interactions with the Ala69-Arg74 dynamic loop. In addition, the structures of the di-metal TnDhp in complexes with hydantoin, N-carbomyl-beta-alanine and N-carbomyl-beta-aminoisobutyrate, as well as apo-TnDhp in complex with a product analog, N-(2-acetamido)-iminodiacetic acid, have been determined. These structural results illustrate how a protein exploits unique lysines and the metal distribution to accomplish lysine carbamylation as well as subsequent enzymatic functions.

Crystal Structures of Vertebrate Dihydropyrimidinase and Complexes from Tetraodon Nigroviridis with Lysine Carbamylation: Metal and Structural Requirements for Post-Translational Modification and Function.,Hsieh YC, Chen MC, Hsu CC, Chan SI, Yang YS, Chen CJ J Biol Chem. 2013 Sep 4. PMID:24005677^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.