title: Crystal structure and molecular modeling study of N-carbamoylsarcosine amidase Ta0454 from Thermoplasma acidophilum.
abstract: A crystal structure of the putative N-carbamoylsarcosine amidase (CSHase) Ta0454 from Thermoplasma acidophilum was solved by single-wavelength anomalous diffraction and refined at a resolution of 2.35A. CSHases are involved in the degradation of creatinine. Ta0454 shares a similar fold and a highly conserved C-D-K catalytic triad (Cys123, Asp9, and Lys90) with the structures of three cysteine hydrolases (PDB codes 1NBA, 1IM5, and 2H0R). Molecular dynamics (MD) simulations of Ta0454/N-carbamoylsarcosine and Ta0454/pyrazinamide complexes were performed to determine the structural basis of the substrate binding pattern for each ligand. Based on the MD-simulated trajectories, the MM/PBSA method predicts binding free energies of -24.5 and -17.1 kcal/mol for the two systems, respectively. The predicted binding free energies suggest that Ta0454 is selective for N-carbamoylsarcosine over pyrazinamide, and zinc ions play an important role in the favorable substrate bound states.
authors.affiliation: School of Pharmaceutical Sciences, East Campus, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Heping
authors.initials: H
authors.lastname: Zheng
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Zimmerman
authors.forename: Maksymilian
authors.initials: M
authors.lastname: Chruszcz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Skarina
authors.forename: Olga
authors.initials: O
authors.lastname: Egorova
authors.forename: Alexei
authors.initials: A
authors.lastname: Savchenko
authors.forename: Aled M
authors.initials: AM
authors.lastname: Edwards
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013822:Thermoplasma / Q000201:enzymology*
chemical_list: D000581:Amidohydrolases; C050011:N-carbamoylsarcosine amidohydrolase