Most well studied heme proteins (globins, c-and b-type cytochromes, peroxidases, P450) all have exactly the same heme prosthetic group yet each exhibits very different and very clearly defined functions. These differences are dictated by interactions between the protein and heme much of which has been deciphered through a variety of spectral probes and x-ray crystallography. The research in this proposal will center on testing hypotheses derived primarily from heme enzyme crystal structures. One question centers on the role that amino acid radicals play in peroxidase catalysis and how the protein environment helps to stabilize a particular Trp radical in cyctohrome c peroxidase. Other questions center on alternate binding sites for peroxidase substrates and mechanisms of inter-protein electron transfer. The primary methods to be employed are protein engineering coupled with crystallography and other biophysical approaches such as EPR spectroscopy and flash photolysis methods for following rapid reactions.
| Poulos, Thomas L (2014) Heme enzyme structure and function. Chem Rev 114:3919-62 |
| Tripathi, Sarvind; O'Neill, Maura J; Wilks, Angela et al. (2013) Crystal structure of the Pseudomonas aeruginosa cytoplasmic heme binding protein, Apo-PhuS. J Inorg Biochem 128:131-6 |
| Jensen, Lyndal M R; Meharenna, Yergalem T; Davidson, Victor L et al. (2012) Geometric and electronic structures of the His-Fe(IV)=O and His-Fe(IV)-Tyr hemes of MauG. J Biol Inorg Chem 17:1241-55 |
| Benabbas, Abdelkrim; Karunakaran, Venugopal; Youn, Hwan et al. (2012) Effect of DNA binding on geminate CO recombination kinetics in CO-sensing transcription factor CooA. J Biol Chem 287:21729-40 |
| Jasion, Victoria S; Poulos, Thomas L (2012) Leishmania major peroxidase is a cytochrome c peroxidase. Biochemistry 51:2453-60 |
| Martell, Jeffrey D; Deerinck, Thomas J; Sancak, Yasemin et al. (2012) Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy. Nat Biotechnol 30:1143-8 |
| Jasion, Victoria S; Doukov, Tzanko; Pineda, Stephanie H et al. (2012) Crystal structure of the Leishmania major peroxidase-cytochrome c complex. Proc Natl Acad Sci U S A 109:18390-4 |
| Jasion, Victoria S; Polanco, Julio A; Meharenna, Yergalem T et al. (2011) Crystal structure of Leishmania major peroxidase and characterization of the compound i tryptophan radical. J Biol Chem 286:24608-15 |
| Meharenna, Yergalem T; Doukov, Tzanko; Li, Huiying et al. (2010) Crystallographic and single-crystal spectral analysis of the peroxidase ferryl intermediate. Biochemistry 49:2984-6 |
| Sundaramoorthy, Munirathinam; Gold, Michael H; Poulos, Thomas L (2010) Ultrahigh (0.93A) resolution structure of manganese peroxidase from Phanerochaete chrysosporium: implications for the catalytic mechanism. J Inorg Biochem 104:683-90 |
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