Editing Kinase (section)

==Biochemistry and functional relevance==
[[File:Basic phosphorylation reaction.png|thumb|upright=3|General reaction that is catalyzed by kinases]]Kinases mediate the transfer of a phosphate moiety from a high energy molecule (such as [[adenosine triphosphate|ATP]]) to their substrate molecule, as seen in the figure below. Kinases are needed to stabilize this reaction because the [[phosphoanhydride]] bond contains a high level of energy. Kinases properly orient their substrate and the phosphoryl group within their active sites, which increases the rate of the reaction. Additionally, they commonly use positively charged [[amino acid]] residues, which electrostatically stabilize the [[transition state]] by interacting with the negatively charged phosphate groups. Alternatively, some kinases utilize bound metal cofactors in their active sites to coordinate the phosphate groups. Protein kinases can be classed as catalytically active (canonical) or as [[Pseudokinase|pseudokinases]], reflecting the evolutionary loss of one or more of the catalytic amino acids that position or hydrolyse ATP.<ref name="pmid24818526">{{cite journal | vauthors = Reiterer V, Eyers PA, Farhan H | title = Day of the dead: pseudokinases and pseudophosphatases in physiology and disease | journal = Trends in Cell Biology | volume = 24 | issue = 9 | pages = 489–505 | date = September 2014 | pmid = 24818526 | doi = 10.1016/j.tcb.2014.03.008 }}</ref> However, in terms of signalling outputs and disease relevance, both kinases and pseudokinases are important signalling modulators in human cells, making kinases important drug targets.<ref>Foulkes DM, Byrne DP and Eyers PA (2017) Pseudokinases: update on their functions and evaluation as new drug targets. Future Med Chem. 9(2):245-265</ref>

Kinases are used extensively to [[signal transduction|transmit signals]] and regulate complex processes in cells. Phosphorylation of molecules can enhance or inhibit their activity and modulate their ability to interact with other molecules. The addition and removal of phosphoryl groups provides the cell with a means of control because various kinases can respond to different conditions or signals. Mutations in kinases that lead to a loss-of-function or gain-of-function can cause cancer<ref>{{cite news| vauthors = Samarasinghe B |title=Hallmarks of Cancer 1|url=http://blogs.scientificamerican.com/guest-blog/2013/09/18/hallmarks-of-cancer-1-self-sufficiency-in-growth-signals|newspaper=Scientific American}}</ref> and disease in humans, including certain types of [[leukemia]] and [[neuroblastoma]]s, [[glioblastoma]],<ref>{{cite journal | vauthors = Bleeker FE, Lamba S, Zanon C, Molenaar RJ, Hulsebos TJ, Troost D, van Tilborg AA, Vandertop WP, Leenstra S, van Noorden CJ, Bardelli A | display-authors = 6 | title = Mutational profiling of kinases in glioblastoma | journal = BMC Cancer | volume = 14 | pages = 718 | date = September 2014 | pmid = 25256166 | pmc = 4192443 | doi = 10.1186/1471-2407-14-718 | doi-access = free }}</ref> [[spinocerebellar ataxia]] (type 14), forms of [[agammaglobulinaemia]], and many others.<ref>{{cite journal | vauthors = Lahiry P, Torkamani A, Schork NJ, Hegele RA | title = Kinase mutations in human disease: interpreting genotype-phenotype relationships | journal = Nature Reviews. Genetics | volume = 11 | issue = 1 | pages = 60–74 | date = January 2010 | pmid = 20019687 | doi = 10.1038/nrg2707 | s2cid = 37398118 }}</ref>