NEGATIVE ELECTROSTATIC SURFACE-POTENTIAL OF PROTEIN SITES SPECIFIC FOR ANIONIC LIGANDS

Determination of the crystal structure of an ''open'' unliganded activ e mutant (T141D) form of the Escherichia coli phosphate receptor for a ctive transport has allowed calculation of the electrostatic surface p otential for it and two other comparably modeled receptor structures ( wild type and D137N). A discovery of considerable implication is the i ntensely negative potential of the phosphate-binding cleft, We report similar findings for a sulfate transport receptor, a DNA-binding prote in, and, even more dramatically, redox proteins, Evidently, for protei ns such as these, which rely almost exclusively on hydrogen bonding fo r anion interactions and electrostatic balance, a noncomplementary sur face potential is not a barrier to binding. Moreover, experimental res ults show that the exquisite specificity and high affinity of tile pho sphate and sulfate receptors for anions are insensitive to modulations of charge potential, but extremely sensitive to conditions that leave a hydrogen bond donor or acceptor unpaired.