Download MendeleyCrystal Structures of the CBS and DRTGG Domains of the Regulatory Region of Clostridiumperfringens Pyrophosphatase Complexed with the Inhibitor, AMP, and Activator, Diadenosine Tetraphosphate.
Tuominen, H., Salminen, A., Oksanen, E., Jamsen, J., Heikkila, O., Lehtio, L., Magretova, N.N., Goldman, A., Baykov, A.A., Lahti, R.(2010) J Mol Biol
- PubMed: 20303981
- DOI: https://doi.org/10.1016/j.jmb.2010.03.019
- Primary Citation of Related Structures:
3L2B, 3L31 - PubMed Abstract:
Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides.
Organizational Affiliation:
Department of Biochemistry and Food Chemistry, University of Turku, Vatselankatu 2, FI-20014 Turku, Finland.
