Very stable ribonucleotide substrate radical relevant for class I ribonucleotide reductase
2000 (English)In: Journal of Physical Chemistry B, ISSN 1089-5647, Vol. 104, no 31, 7502-7509 p.Article in journal (Refereed) Published
In recent experimental studies on the E441Q mutant of ribonucleotide reductase, a new substrate radical was discovered on the minute time scale. This radical is kinetically coupled to a cysteine-based radical appearing on the 10 s time scale. In the present study, density functional calculations have been performed to investigate the nature of these radicals. The most interesting result is that a very stable substrate radical was found, which lies outside the normal substrate pathway. This radical is so stable that its creation has to be avoided by the enzyme, or the substrate reactions would be slowed by several orders of magnitude. It is suggested that the enzyme accomplishes this task by considerably straining the mobility of the Cys225 residue. A previously suggested reaction mechanism is modified to take these recent findings into account. The modification does not significantly change the energetics of the model reactions.
Place, publisher, year, edition, pages
2000. Vol. 104, no 31, 7502-7509 p.
active-site, protein r1, mechanism, mutant, e441q, model
IdentifiersURN: urn:nbn:se:kth:diva-19958ISI: 000088683700039OAI: oai:DiVA.org:kth-19958DiVA: diva2:338650
QC 201005252010-08-102010-08-10Bibliographically approved