Nickel binding to the N-tail of histone H4: an NMR study

glh International Symposium on Metal lons in Biology and Medicine Book of Abatracta

9

th

INTERNATIONAL SYMPOSIUM

ON MET AL IONS IN

BIOLOGY AND MEDICINE

May, 21-24, 2006

Centro de Congressos da Universidade Cat6lica

Lisboa, Portugal

Capa: Concepçào do Gabinete de Imagem da Universidade de Coimbra

Titulo: Metallons Role in Life: An Integrated View

I mpressao e acabamentos:

Redhorse - Industria Grafica, Lda Rua Casal dos Vagares - Alto de S Joào

Tel: 230702210

Fax: 239701239

glh International Symposium on Metal lons in Biology and Medicine Book of Abstracts

NICKEL BINDING TO THE N-TAIL OF HISTONE H4: AN NMR STUDY Zoroddu M. A., Peana M., Medici S.

Unil'(',-sity ofSassari. Deparlmenf olChemislfy. /'ia Vienna 2, 07100 Sassori. IlalrEmoil:

=oroddll@lIniss.il

0-46

Nickel has been shown to be an essential trace element involved in the metabolism of severa! species of bacteria, archea. pianI and may yet be found to play a role in the metaholism of higher organisms. However. thc carcinogcnicity of certain nickel compounds has been confirmcd

by

the combination

or

epidemiological evidence in humans and carcinogenesis bioassays in animals. Thc molccular mechanisrns

or

nickel-induced carcinogenesis include interactions of this metal with major chromatin

componcnts causing allerations in gene expression rather than by direct DNA

damage. We have previously reported that nickel is a potenl suppressor of histone 1-14 acctylation. in both yeasl and mammalian cells. Il has prelèrence to specific Iysinc rcsiducs in the N-terminai tail of histone 1-14. in which the siles of acetylation are clusLercd.

l-Icre wc prcsent our recenl resuhs on Lhe coordinaLion abiliL)' of Ni (H) to the N -terminai lail orhistone 1-14 using NMR spcctroscopy. A series of ID, 2D Tocsy and Noesy 1)_, NMR spectra of the lail with increasing nickel concenlration to the final

molar ratio l: l, were acquired, and thc data wc collCClcd allowed us to ca1culate a structural model for thc squarc planar complex formcd by the Ni(lI) ion and our peptide, confirming that the N-terminai lail of histonc '-14 is a suitable binding site for Nickel ions.