Vullo Daniela, Del Prete Sonia, Capasso Clemente, Supuran Claudiu T
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Istituto di Biochimica delle Proteine-CNR, Via P. Castellino 111, 80131 Napoli, Italy; Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
Bioorg Med Chem Lett. 2016 Mar 1;26(5):1381-5. doi: 10.1016/j.bmcl.2016.01.078. Epub 2016 Jan 29.
The β-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D-DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3μM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl-alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9μM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81μM. This study may help a better understanding of the activation mechanisms of β-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents.
对来自产生头皮屑的真菌球形马拉色菌的β-碳酸酐酶(CA,EC 4.2.1.1),即MgCA,进行了其与胺类和氨基酸的激活作用研究。MgCA被L-/D-组氨酸、L-苯丙氨酸、D-多巴、D-色氨酸、L-/D-酪氨酸等氨基酸以及胺类血清素(解离常数KAs为12.5 - 29.3μM)微弱激活,但被d-苯丙氨酸、l-多巴、l-色氨酸、组胺、多巴胺、吡啶基烷基胺和4-(2-氨基乙基)吗啉更有效地激活,解离常数KAs为5.82 - 10.9μM。最佳激活剂是l-肾上腺素和1-(2-氨基乙基)哌嗪,激活常数为0.72 - 0.81μM。这项研究可能有助于更好地理解致病真菌中β-碳酸酐酶的激活机制,以及设计与该酶结合更紧密的配体,该酶是新型去屑剂的药物靶点。