The ubiquitous roles of cytochrome P450 proteins

摘要: Looking across the tree of life, it is amazing to find cytochrome P450 proteins represented in all life forms. Volume 3, devoted solely vital and still expanding research area concerning P450s, offers 17 stimulating chapters written by 36 internationally recognized experts an authoritative timely account this fascinating subject. The Ubiquitous Roles Cytochrome Proteins highlights, supported nearly 2700 references, more than 20 tables 190 illustrations, function these versatile catalysts which act as monooxygenases insert oxygen atom from dioxygen into a substrate molecule oxidizing it. P450s are important biosynthesis hormones signaling molecules well xenobiotic metabolism detoxification ranging pharmaceuticals humans toxic substances insects plants. Mechanistic aspects design engineering systems for biotechnological applications also covered. MILS-3 essential scientists working wide range bioinorganic chemistry way through medicine including clinic. This volume encompasses breadth efforts focused on structure appreciation diversity complexity biotransformations they catalyze. introductory Chapter 1, setting scene, explores many different levels at enzymes (and their respective genes) have diverged process evolution yield plethora that now termed "P450 monooxygenases". broad unprecedented reactivity contain heme iron center (most commonly iron(III)protoporphyrin IX) with deprotonated cysteine side chain providing fifth ligand iron, has challenged "biomimetic community". Indeed, much been accomplished over past five decades, e.g., regarding understanding unusual activation paramagnetic reductive cleavage, evident 2 provides depth overview structural functional mimics P450s. structures molecular phylogeny detailed together nomenclature classification. It made clear protein fold unique highly conserved independent organism; astonishingly, same used some catalyze non-P450 redox transformations. worthwhile note extremes pH heat, was recently discovered archaeans. reflected aquatic species outlined 4 where expecially activities invertebrates focus. 5 examines ability electrochemical techniques unravel fundamental electron transfer enzymes. central catalysis thus, 6 extensive studies summarized shown interprotein facilitated proper positioning, flavin mononucleotide- heme-containing domains. Clearly, generation truly catalytic system utilizes non-native cofactors place reductase holy grail research. next four mechanistic considerations: At first leakage reactions considered occur during cycle, followed evaluations basis recognition catalysis, architecture active site. secondary coordination sphere, i.e., proximal (thiolate) distal (where binding occurs) described next, several small-molecule inhibitors like nitrogen monoxide (nitric oxide), carbon monoxide, cyanide, imidazole. P450-catalyzed hydroxylations epoxidations, steroid hormones, catalyzed carbon-carbon bond cleavage discussed Chapters 11–13. 14 oxidation non-natural substrates. Evidently, potential altered environmentally benign synthesis chemical products intermediates expected area. In terminating three biotransformation xenobiotics comprehensively dealt with, "chemical defence" or response organism foreign chemicals. Thereafter drugs human described, particular significance drug development finally daily clinic, emphasized clinical pharmacist.