Allosteric inhibitors of plasma membrane Ca²⁺ pumps: Invention and applications of caloxins

• 作者: Ashok K Grover Jyoti Pande M Szewczyk
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 生物学
• 关键词: PHAGE display Calcium signaling Plasma membrane Ca2+pumps Hypertension Neuronal disorders CONTRACEPTION Cancer Thrombosis Lipid RAFTS
• 年，卷（期）: 2011,（3）
• 页码范围: 39-47
• 页数: 9页
• 分类号: Q73

摘要

Plasma membrane Ca2+pumps(PMCA)play a major role in Ca2+homeostasis and signaling by extruding cellular Ca2+with high affinity.PMCA isoforms are encoded by four genes which are expressed differentially in various cell types in normal and disease states.Therefore, PMCA isoform selective inhibitors would aid in delineating their role in physiology and pathophysiology.We are testing the hypothesis that extracellular domains of PMCA can be used as allosteric targets to obtain a novel class of PMCA-specific inhibitors termed caloxins. This review presents the concepts behind the invention of caloxins and our progress in this area.A section is also devoted to the applications of caloxins in literature. We anticipate that isoform-selective caloxins will aid in understanding PMCA physiology in health and disease. With strategies to develop therapeutics from bioactive peptides,caloxins may become clinically useful in car diovascular diseases,neurological disorders,retinopathy,cancer and contraception.