Mutation, designation

Further understanding of i gene function has come from study of rare mutations designated t. Mutants bearing... 

Murchison, H. A., Alden, R. A., Allen, J. P., Peloquin, J. M., Taguchi, A. K. W., Woodbury, N. W., and Williams, J. C., 1993, Mutations designed to modify fhe environmenf of fhe primary electron donor of the reaction center from Rhodobacter sphaeroides Phenylalanine to leucine at L167 and histidine to phenylalanine at L168. Biochemistry, 32 34989 3505. 

Assfalg et have determined the solution structure of enriched yeast iso-l-ferricytochrome c which contained three mutations designed to produce a single conformer. The global structure of the protein was determined using NOE s, backbone angle constraints, and pseudocontact shifts as constraints. Yao et have determined the solution structure of cyanoferricytochrome c. 

We changed our hypothesis and then found success. C. S. Lengyel et al. Mutations designed to destabilize the receptor-bound conformation increase MICA-NKG2D association rate and affinity. 2007. / Biol Chem. 282(42), p. 30658. 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

Mutations in the specificity pocket of trypsin, designed to change the substrate preference of the enzyme, also have drastic effects on the catalytic rate. These mutants demonstrate that the substrate specificity of an enzyme and its catalytic rate enhancement are tightly linked to each other because both are affected by the difference in binding strength between the transition state of the substrate and its normal state. 

Nicholson, H., Becktel, W.J., Matthews, B.W. Enhanced protein thermostability from designed mutations that interact with a-helix dipoles. Nature 336 651-656, 1988. 

Common to all three aims is that silico-derived predictions can rationalize experimental efforts either by well-directed very specific molecular biological experiments like site directed mutations or e.g., by reducing the number of compounds to screen experimentally for drug design. 

These examples are part of a broader design scheme to combine catalytic metal complexes with a protein as chiral scaffold to obtain a hybrid catalyst combining the catalytic potential of the metal complex with the enantioselectivity and evolvability of the protein host [11]. One of the first examples of such systems combined a biotinylated rhodium complex with avidin to obtain an enantioselective hydrogenation catalyst [28]. Most significantly, it has been shovm that mutation-based improvements of enantioselectivity are possible in these hybrid catalysts as for enzymes (Figure 3.7) [29]. 

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