Sy. Guo et al., CIS-ACTIVE RAS G2-LIKE SEQUENCE IMPLICATED IN THE HETEROTROPIC ACTIVATION OF THE DEOXYADENOSINE KINASE OF LACTOBACILLUS-ACIDOPHILUS R-26, The Journal of biological chemistry, 272(11), 1997, pp. 6890-6897
Deoxyadenosine kinase (dAK) forms a heterodimer with either deoxyguano
sine kinase (dGK) or deoxycytidine kinase (dCK), and is heterotropical
ly activated 3-5 times by dGuo or dCyd. Expressed alone, dAK is inacti
ve and exhibits no response to dGuo or dCyd; activity and heterotropic
response are fully restored upon reassociation with dGK or dCK. Howev
er, turnover of independently expressed dGK or dCK: is nearly maximal,
being further activated only 50-100% upon reassociation with dAK, In
neither case is the heterotropic activation due to ligand-induced hete
rodimer formation. A proline/alanine substitution within a dAK segment
homologous to loop G2 of Has proteins yielded a heterodimer with dAK
permanently cis-activated a-fold, with a corresponding reduction in he
terotropic activation by dGuo, A chimeric dAK, with 25% of its C termi
nus substituted by the homologous sequence from dGK, was inactive alon
e, and its characteristics were unchanged in the reconstituted heterod
imer, Superimposing the Pro/Ala substitution on this chimera also redu
ced heterotropic activation by half, Cross-linking the dimer by 1,5-di
fluoro-2,4-dinitrobenzene was inhibited by ATP, dATP, dGTP, and dAdo,
suggesting the proximity of the active site(s) to the interface, These
data suggest that dAK depends on dGK or dCK in a manner resembling th
e reliance of Has upon GTPase activating protein.