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Publication Abstract from PubMed

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.

Crystal structure and molecular modeling study of N-carbamoylsarcosine amidase Ta0454 from Thermoplasma acidophilum.,Luo HB, Zheng H, Zimmerman MD, Chruszcz M, Skarina T, Egorova O, Savchenko A, Edwards AM, Minor W J Struct Biol. 2010 Mar;169(3):304-11. Epub 2009 Nov 20. PMID:19932181^[1]

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