4LCS

The crystal structure of di-Zn dihydropyrimidinase in complex with hydantoin

Summary for 4LCS

• Entry DOI: 10.2210/pdb4lcs/pdb
• Related: 4GZ7 4H00 4H01 4LCQ 4LCR
• Descriptor: Chromosome 8 SCAF14545, whole genome shotgun sequence, ZINC ION, imidazolidine-2,4-dione, ... (4 entities in total)
• Functional Keywords: hydrolase, zinc binding, carboxylation, alpha-beta barrel, hydrolase activator
• Biological source: Tetraodon nigroviridis (Spotted green pufferfish)
• Total number of polymer chains: 1
• Total formula weight: 57161.26

Authors

Hsieh, Y.C.,Chen, M.C.,Hsu, C.C.,Chan, S.I.,Yang, Y.S. (deposition date: 2013-06-23, release date: 2013-09-18, Last modification date: 2025-03-26)

Primary citation

Hsieh, Y.C.,Chen, M.C.,Hsu, C.C.,Chan, S.I.,Yang, Y.S.,Chen, C.J.
Crystal structures of vertebrate dihydropyrimidinase and complexes from Tetraodon nigroviridis with lysine carbamylation: metal and structural requirements for post-translational modification and function.
J.Biol.Chem., 288:30645-30658, 2013

PubMed Abstract: 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 apoenzyme as well as two forms of the holoenzyme with one and two metals at the catalytic site. The essential active-site structural requirements have been identified for the 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, Ala(69)-Arg(74) and Met(158)-Met(165), 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 monometal TnDhp, and in the "closed form" in the dimetal TnDhp structure, respectively. Structural comparison also suggests that the C-terminal tail plays a role in the enzymatic function through interactions with the Ala(69)-Arg(74) dynamic loop. In addition, the structures of the dimetal TnDhp in complexes with hydantoin, N-carbamyl-β-alanine, and N-carbamyl-β-amino isobutyrate 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.

PubMed: 24005677
DOI: 10.1074/jbc.M113.496778

Experimental method

X-RAY DIFFRACTION (2.2 Å)