6LZO
Thermolysin with 1,10-phenanthroline
Summary for 6LZO
| Entry DOI | 10.2210/pdb6lzo/pdb |
| Descriptor | Thermolysin, CALCIUM ION, 1,10-PHENANTHROLINE, ... (4 entities in total) |
| Functional Keywords | thermolysin, metalloproteinase, hydrolase |
| Biological source | Bacillus thermoproteolyticus |
| Total number of polymer chains | 1 |
| Total formula weight | 35701.93 |
| Authors | Nam, K.H. (deposition date: 2020-02-19, release date: 2021-01-27, Last modification date: 2023-11-29) |
| Primary citation | Nam, K.H. Structural analysis of metal chelation of the metalloproteinase thermolysin by 1,10-phenanthroline. J.Inorg.Biochem., 215:111319-111319, 2021 Cited by PubMed Abstract: Metalloproteases and their inhibitors are important in numerous fundamental biochemical phenomena and medical applications. The heterocyclic organic compound, 1,10-phenanthroline, forms a complex with transition metal ions and is a Zn-chelating metalloprotease inhibitor; however, the mechanism of 1,10-phenanthroline-based chelation inhibition has not been fully elucidated. This study aimed to understand the structural basis of zinc metalloproteinase inhibition by 1,10-phenanthroline. Herein, the crystal structure of thermolysin was determined in the absence and presence of 1,10-phenanthroline at 1.5 and 1.8 Å, respectively. In native thermolysin, Zn at the active site is tetrahedrally coordinated by His142, His146, Glu166, and water molecule and contains three Ca ions, which are involved in thermostability. In the crystal structure of 1,10-phenanthroline-treated thermolysin crystal, seven 1,10-phenanthroline molecules were observed on the surface of thermolysin. These molecules are stabilized by π- π stacking interactions with aromatic amino acids (Phe63, Tyr66, Tyr110, His216, and Try251) or between the 1,10-phenanthrolines. Moreover, interactions with Ser5 and Arg101 were also observed. In this structure, Zn at the active site was completely chelated, but no large conformational changes were observed in Zn coordination with amino acid residues. Ca at the Ca3 site exposed to the solvent was chelated by 1,10-phenanthroline, resulting in a conformational change in the side chain of Asp56 and Gln61. Based on the surface structure, for 1,10-phenanthroline to chelate a metal, it is important that the metal is exposed on the protein surface and that there is no steric hindrance impairing 1,10-phenanthroline access by the amino acids around the metal. PubMed: 33310458DOI: 10.1016/j.jinorgbio.2020.111319 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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