title: Drug discovery targeting heme-based sensors and their coupled activities.
abstract: Heme-based sensors have emerged during the last 20years as being a large family of proteins that occur in all kingdoms of life. A myriad of biological adaptations are associated with these sensors, which include vasodilation, bacterial virulence, dormancy, chemotaxis, biofilm formation, among others. Due to the key activities regulated by these proteins along with many other systems that use similar output domains, there is a growing interest in developing small molecules as their regulators. Here, we review the development of potential activators and inhibitors for many of these systems, including human soluble guanylate cyclase, c-di-GMP-related enzymes, Mycobacterium tuberculosis DevR/DevS/DosT (differentially expressed in virulent strain response regulator/sensor/dormancysurvival sensorT), the Rev-erb-α and β nuclear receptor, among others. The possible roles of these molecules as biochemical tools, therapeutic agents, and novel antibiotics are critically examined.
authors.affiliation: Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Center for Sciences, Fortaleza, Ceara 60440-900, Brazil. Electronic address: eduardohss@dqoi.ufc.br.
authors.forename: Eduardo Henrique Silva
authors.initials: EH
authors.lastname: Sousa
authors.affiliation: Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Center for Sciences, Fortaleza, Ceara 60440-900, Brazil.
authors.forename: Luiz Gonzaga de França
authors.initials: LG
authors.lastname: Lopes
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA. Electronic address: marie-alda.gilles-gonzalez@utsouthwestern.edu.
authors.forename: Marie-Alda
authors.initials: MA
authors.lastname: Gilles-Gonzalez
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D015374:Biosensing Techniques / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006418:Heme; D006801:Humans; D009169:Mycobacterium tuberculosis; D000071756:Soluble Guanylyl Cyclase / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D006418:Heme; D000071756:Soluble Guanylyl Cyclase
keywords: Drug discovery; Heme-based sensor; Histidine protein kinase; Nuclear receptor; Nucleotide cyclase; Phosphodiesterase