On the contribution of stereochemistry to human ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrate


Autoria(s): Riley, Andrew M; Deleu, Sandrine; Qian, Xun; Mitchell, Jennifer; Chung, Sung-Kee; Adelt, Stephan; Vogel, Günter; Potter, Barry V L; Shears, Stephen B
Data(s)

2006

Resumo

Ins(1,4,5,6)P4, a biologically active cell constituent, was recently advocated as a substrate of human Ins(3,4,5,6)P4 1-kinase (hITPK1), because stereochemical factors were believed relatively unimportant to specificity [Miller, G.J. Wilson, M.P. Majerus, P.W. and Hurley, J.H. (2005) Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-triphosphate 5/6-kinase. Mol. Cell. 18, 201-212]. Contrarily, we provide three examples of hITPK1 stereospecificity. hITPK1 phosphorylates only the 1-hydroxyl of both Ins(3,5,6)P3 and the meso-compound, Ins(4,5,6)P3. Moreover, hITPK1 has >13,000-fold preference for Ins(3,4,5,6)P4 over its enantiomer, Ins(1,4,5,6)P4. The biological significance of hITPK1 being stereospecific, and not physiologically phosphorylating Ins(1,4,5,6)P4, is reinforced by our demonstrating that Ins(1,4,5,6)P4 is phosphorylated (K(m) = 0.18 microM) by inositolphosphate-multikinase.

info:eu-repo/semantics/published

Formato

1 full-text file(s): application/pdf

Identificador

uri/info:doi/10.1016/j.febslet.2005.12.016

uri/info:pii/S0014-5793(05)01475-4

uri/info:pmid/16376887

https://dipot.ulb.ac.be/dspace/bitstream/2013/229471/3/Elsevier_213098.pdf

http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/229471

Idioma(s)

en

Fonte

FEBS letters, 580 (1

Palavras-Chave #Sciences bio-médicales et agricoles #Humans #Inositol Phosphates -- chemistry #Molecular Structure #Phosphotransferases (Alcohol Group Acceptor) -- chemistry #Stereoisomerism #Structure-Activity Relationship #Substrate Specificity
Tipo

info:eu-repo/semantics/article

info:ulb-repo/semantics/articlePeerReview

info:ulb-repo/semantics/openurl/article

Direitos

1 full-text file(s): info:eu-repo/semantics/restrictedAccess