Electrostatic guidance

ED Getzoff, DE Cabelli, CL Fisher, HE Parge, MS Viezzoli, L Banci, RA Hallewell. Faster superoxide dismutase mutants designed by enhancing electrostatic guidance. Nature 358 347-351, 1992. 

B. Facilitated Encounter of 05 with the Active Site by Electrostatic Guidance... 

The discussion here is limited to CuZnSOD for a number of reasons. First, in this system the ping-pong mechanism described in reactions (22) and (23) is operative as written whereas both MnSOD and FeSOD carry out catalysis by mechanisms that involve observable enzyme-substrate complexes under certain conditions. Secondly, this enzymatic system has been studied as a model to look at such factors as electrostatic guidance of substrate (see below). Finally, the link that was demonstrated between over 100 point mutations in CuZnSOD and the inherited version of amyotrophic lateral sclerosis (Lou Gehrig s Disease) has made underscored the importance in understanding details of enzyme function. ... 

Bacterial ( . coli) CuZnSOD lacks most of the charged residues critical for electrostatic guidance of the substrate but has a compensatory and functionally equivalent mechanism contributed by Lys 60 providing a reaction rate constant, (1.4 0.1)xl0 M" s not much lower than mammalian enzymes [50]. 

E. D. Getzoff, D. E. Cabelli, C. L. Fisheii H. E. Parge, M. S. Viezzoli, L. Banci, and R. A. Hallewell, Nature, 358, 347 (1992). Faster Superoxide Dismutase Mutants Designed by Enhancing Electrostatic Guidance. 

L. Hallewell, R. A. (1992). Faster superoxide dismutase mutants designed by enhandng electrostatic guidance. Nature (London), 358, 347-51. 

Cytochrome c + cytochrome c peroxidase Electrostatic guidance. Effects of single-point mutations significant and qualitatively similar to experimental data. Fluctuations of the encounter complex simulated by MD lead to differences in rate smaller than errors in computed rates. Two distinct binding orientations/domains consisting of many conformations. 75,76... 

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