Differential 3-bromopyruvate inhibition of cytosolic and mitochondrial human serine hydroxymethyltransferase isoforms, key enzymes in cancer metabolic reprogramming
详细信息 查看全文
- 作者：Alessandro Paiardinia ; 1 ; Angela Tramontib ; c ; 1 ; Doug Schirchd ; Giulia Guiduccic ; Martino Luigi di Salvoc ; Alessio Fiascarellic ; Alessandra Giorgic ; Bruno Marasc ; Francesca Cutruzzolà ; c ; francesca.cutruzzola@uniroma1.it" class="auth_mail" title="E-mail the corresponding author ; Roberto Contestabilec ; roberto.contestabile@uniroma1.it" class="auth_mail" title="E-mail the corresponding author
- 关键词：SHMT ; serine hydroxymethyltransferase ; SHMT1 ; cytosolic SHMT ; SHMT2 ; mitochondrial SHMT ; 3BP ; 3-bromopyruvate ; PLP ; pyridoxal 5&prime ; -phosphate ; H4PteGlu ; tetrahydropteroylglutamate
- 刊名：Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
- 出版年：2016
- 出版时间：November 2016
- 年：2016
- 卷：1864
- 期：11
- 页码：1506-1517
- 全文大小：1681 K
文摘
- •
3-Bromopyruvate completely inhibits SHMT1, alkylating the active site Cys204.
- •
SHMT2, which lacks Cys 204, is only partially inhibited by 3-bromopyruvate.
- •
3-Bromopyruvate binds to SHMT1 active site forming a non-covalent complex.
- •
Introducing a Cys residue in SHMT2 active site yields a complete inhibition.
- •
3-Bromopyruvate is a lead compound for the design of selective SHMT1 inhibitors.