Lanthanide ions inhibit the activity of dihydrofolate reductase from chicken liver

Content Provider	Semantic Scholar
Author	Wu, Ying Ping
Copyright Year	2004
Abstract	The influences of mono-, bi- and trivalent metal ions (as chloride salts) on the activity of dihydrofolate reductase (DHFR) from chicken liver have been studied to elucidate the mechanism of ion-activation of this enzyme. The results show that monovalent ions (Na+ and K+) activate DHFR at low concentration reaching a maximum activation of about 2.5 fold at 0.4–0.5 M and declining at higher concentrations. Ca2+ shows similar activation but at lower concentration, reaching a maximum at 0.1 M; activity declines with further increases in concentration. At very high concentration (> 0.4 M), Ca2+ is inhibitory. The trivalent lanthanide ions, however, show a dramatic inhibition of activity of DHFR even at very low concentration. The activity of DHFR declines to 50% of that of the control at 0.02 mM EuCl3. Intrinsic fluorescence measurements show that the ion-dependent activation in the presence of mono- and bivalent metal ions is due to the conformational changes in the protein. Energy transfer phenomenon suggests that the specific interaction of Eu3+ with Trp24 located in a loop at the active site of DHFR is responsible for the strong inhibition. The possible mechanism for the ion-inhibition is proposed and discussed.
Starting Page	195
Ending Page	201
Page Count	7
File Format	PDF HTM / HTML
DOI	10.1023/A:1009220311261
PubMed reference number	11127890
Journal	Medline
Volume Number	13
Alternate Webpage(s)	http://library.ibp.ac.cn/html/slwj/000165088300001.pdf
Alternate Webpage(s)	https://doi.org/10.1023/A%3A1009220311261
Journal	Biometals
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article