Crystal structure and molecular modeling study of N-carbamoylsarcosine amidase Ta0454 from Thermoplasma acidophilum.
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.
Luo
Hai-Bin
HB
School of Pharmaceutical Sciences, East Campus, Sun Yat-Sen University, Guangzhou 510006, China.
Zheng
Heping
H
Zimmerman
Matthew D
MD
Chruszcz
Maksymilian
M
Skarina
Tatiana
T
Egorova
Olga
O
Savchenko
Alexei
A
Edwards
Aled M
AM
Minor
Wladek
W
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*
D000581:Amidohydrolases; C050011:N-carbamoylsarcosine amidohydrolase