Theoretical Studies of the Catalytic Mechanism of the Dihydroxyacetone Kinase

Dihydroxyacetone kinases (DHAKs) catalyse the transfer of the phosphoryl group from adenosine triphosphate (ATP) to dihydroxyacetone (Dha) generating Dha phosphate (Dha-P), a very important specie for C-C bond formation in nature. Kinases are present in humans and they are involved in cancer progres...

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Detalles Bibliográficos
Autor: Bordes Pastor, Isabel
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/436901
Acceso en línea:http://hdl.handle.net/10803/436901
http://dx.doi.org/10.6035/14026.2017.149273
http://mediaserver.csuc.cat/tdx/documents/40/84/98/4084984048396410099845584293785676930/
Access Level:acceso abierto
Palabra clave:Dihidroxiacetona quinasa
Catálisis
Polifosfato inorgánico
Adenosín trifosfato
QM/MM
Fosfato
Química
544
Descripción
Sumario:Dihydroxyacetone kinases (DHAKs) catalyse the transfer of the phosphoryl group from adenosine triphosphate (ATP) to dihydroxyacetone (Dha) generating Dha phosphate (Dha-P), a very important specie for C-C bond formation in nature. Kinases are present in humans and they are involved in cancer progression, inflammation and autoimmune disorders. In this Doctoral Thesis, it has been studied the molecular mechanism of the phosphoryl transfer from ATP to Dha in aqueous solution and in the DHAK of Escherichia coli employing the quantum mechanical/molecular mechanical (QM/MM) hybrid methodology. In addition, in collaboration with a experimental group of Madrid, it has been performed the tuning of the phosphoryl donor specificity in the DHAK from Citrobacter freundii, from ATP to inorganic polyphosphate, a very advantageous compound. It has been analyzed the binding effects of this compound with the enzyme and also the chemical reaction with the Dha.