Paper Citing NAMD - Abstract
Madrona, Yarrow; Hollingsworth, Scott A.; Tripathi, Sarvind; Fields, James B.; Rwigema, Jean-Christophe N.; Tobias, Douglas J.; Poulos, Thomas L.
Crystal Structure of Cindoxin, the P450cin Redox Partner
BIOCHEMISTRY, 53:1435-1446, MAR 11 2014
The crystal structure of the flavin mononucleotide (FMN)-containing redox partner to P450cin, cindoxin (Cdx), has been determined to 1.3 angstrom resolution. The overall structure is similar to that of the FMN domain of human cytochrome P450 reductase. A Brownian dynamics-molecular dynamics docking method was used to produce a model of Cdx with its redox partner, P450cin. This Cdx-P450cin model highlights the potential importance of Cdx Tyr96 in bridging the FMN and heme cofactors as well P450cin Arg102 and Arg346. Each of the single-site Ala mutants exhibits similar to 10% of the wild-type activity, thus demonstrating the importance of these residues for binding and/or electron transfer. In the well-studied P450cam system, redox partner binding stabilizes the open low-spin conformation of P450cam and greatly decreases the stability of the oxy complex. In sharp contrast, Cdx does not shift P450cin to a low-spin state, although the stability of oxy-P450cin is decreased 10-fold in the presence of Cdx. This indicates that Cdx may have a modest effect on the open-closed equilibrium in P450cin compared to that in P450cam. It has been postulated that part of the effector role of Pdx on P450cam is to promote a significant structural change that makes available a proton relay network involving Asp251 required for O-2 activation. The structure around the corresponding Asp in P450cin, Asp241, provides a possible structural reason for why P450cin is less dependent on its redox partner for functionally important structural changes.
