Structural features of mammalian histidine decarboxylase reveal the basis for specific inhibition.
For a long time the structural and molecular features of mammalian histidine decarboxylase (EC 4.1.1.22), the enzyme that produces histamine, have evaded characterization. We overcome the experimental problems for the study of this enzyme by using a computer-based modelling and simulation approach, and have now the conditions to use histidine decarboxylase as a target in histamine pharmacology. In this review, we present the recent (last 5 years) advances in the structure-function relationship of histidine decarboxylase and the strategy for the discovery of new drugs.
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, Málaga, Spain.
A A
AA
Moya-García
A
A
Pino-Angeles
R
R
Gil-Redondo
A
A
Morreale
F
F
Sánchez-Jiménez
D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D004791:Enzyme Inhibitors; D008024:Ligands; D006640:Histidine Decarboxylase