In DDAH, Zinc (Zn2+) acts as an endogenous inhibitor and prevents normal NOS activity. The Zn(II)-binding site is located inside the protein’s active site, which makes it a competitive inhibitor. It was found that Cys273, His172, Glu77, Asp78, and Asp 268 all play a role in the binding of Zn(II). Cys273 directly coordinates with the Zn(II) ion in the active site while the other significant residues stabilize the ion via hydrogen bonding interactions with water molecules in the active site. Depending on pH, His172 can change conformations and use the imidazole group to directly coordinate the Zn(II) ion. Cys273, which is conserved between bovine and humans, is the key active site residue that coordinates Zn(II). Zinc-cysteine complexes have been found to be important mediators of protein catalysis, regulation, and structure. Cys273 and the water molecules stabilize the Zn(II) ion in a tetrahedral environment. The Zn(II) dissociation constant is 4.2 nM which is consistent with the nanomolar concentrations of Zn(II) in the cells, thus provides more evidence for the regulatory use of Zn(II) by DDAH.
This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
↑Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:https://dx.doi.org/10.1002/ijch.201300024
↑Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
