Abstract:
:EF-hand Ca(II) binding sites share a conserved architecture and are prevalent in Ca(II) signaling pathways. The ion binding kinetics of these sites are carefully tuned to provide the physiologically appropriate activation and inactivation time scales. Here we examine kinetic tuning by the side chain at the ninth position of the EF-loop. A model is proposed in which both the size and charge of the side chain contribute to kinetic tuning. To test this model, the ninth loop position of the EF-hand-like site in the Escherichia coli D-galactose binding protein has been engineered and the Tb(III) dissociation kinetics of the resulting sites have been analyzed. Substitutions at this position are observed to generate up to 10(4)-fold changes in Tb(III) dissociation rates, with little effect on Tb(III) affinity. Furthermore, the observed pattern of rate changes confirm the model's predictions; long side chains at the ninth loop position yield slow dissociation kinetics as predicted for a steric block, whereas acidic side chains yield slow dissociation kinetics as expected for an electrostatic barrier.
journal_name
Proc Natl Acad Sci U S Aauthors
Renner M,Danielson MA,Falke JJdoi
10.1073/pnas.90.14.6493subject
Has Abstractpub_date
1993-07-15 00:00:00pages
6493-7issue
14eissn
0027-8424issn
1091-6490journal_volume
90pub_type
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