title: Molecular analysis of some camel cytochrome P450 enzymes reveals lower evolution and drug-binding properties.
abstract: Camels bear unique genotypes and phenotypes for adaptation of their harsh environment. They have unique visual systems, sniffing, water metabolism, and heat-control mechanisms that are different from other creatures. The recent announcement for the complete sequence of camel genome will allow for the discovery of many secrets of camel life. In this context, the genetic bases of camel drug-metabolizing enzymes are still unknown. Furthermore, the genomic content of camel that rendered it highly susceptible to some drugs (as monensin and salinomycin) and became easily intoxicated needs to be investigated. The objectives of this work are the annotation of camel genome and retrieval of camel for cytochrome P450 (CYP) 1A1, 2C, and 3A enzymes. This is followed by comprehensive phylogenetic, evolution, molecular modeling, and docking studies. In comparison with the human enzymes, camel CYPs showed lower evolution rate, especially CYP1A1. Furthermore, the binding of monensin, salinomycin, alfa-naphthoflavone, felodepine, and ritonavir was weaker in camel enzymes. Interestingly, rerank score indicated instable binding of monensin and salinomycin with camel CYP1A1 as well as salinomycin with camel CYP2C. The results of this work suggest that camels are more susceptible to toxicity with compounds undergoing metabolic oxidation. This conclusion was based on lower evolution rate and lower binding potency of camels compared with the human enzymes.
authors: a Faculty of Veterinary Medicine and Animal Resources , King Faisal University , Alhofuf, Alahsa , Saudi Arabia.
authors: Yousef
authors: Y
authors: Altaher
authors: b Faculty of Veterinary Medicine and Animal Resources, Department of Physiology, Biochemistry and Pharmacology , King Faisal University , Alhofuf, Alahsa , Saudi Arabia.|c Faculty of Veterinary Medicine, Department of Pharmacology , Kafrelshikh University , Kafrelshikh 33516 , Egypt.
authors: Mahmoud
authors: M
authors: Kandeel
mesh_terms: D000818:Animals; D002162:Camelus / Q000235:genetics* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016678:Genome; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D058977:Molecular Sequence Annotation; D008985:Monensin / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D014867:Water / Q000378:metabolism; D000095662:Polyether Polyketides
chemical_list: D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System; D008985:Monensin; D011714:Pyrans; D014867:Water; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: camel; cytochrome P450; docking; molecular modeling; phylogenetics