It wasn't long after scientists finally accepted the radical notion that enzymes were proteins (when James Sumner, who first crystallized an enzyme, mentioned this fact to The Svedberg during a visit to Uppsala, Svedberg called security because Sumner was obviously a dangerous lunatic; Sumner actually had to win the Nobel Prize before he was elected to the US National Academy of Sciences) that the first crystal structure of an enzyme, hen egg white lysozyme, was determined by David Phillips and his associates. By that time mechanistic enzymology was becoming established as an offshoot of physical organic chemistry, and it took years before enzymologists were persuaded that structures of enzymes in "the solid state" had anything to teach them about how these remarkable catalysts worked. Acceptance came in no small part due to the efforts of Dagmar Ringe, who with patience and good humor won over the leading figures in the field, Bill Jencks and Bob Abeles. The Protein Data Bank played a major role in the subsequent explosive growth of structural enzymology, as shown in 2000 when this author, Dagmar, and their associates determined the structures of every kinetically-significant intermediate in the catalytic pathway of cytochrome P450: they could choose the best protein for this project without having to solve the structure of the enzyme first, because its structure was already in the PDB. Although 55+ years of structural enzymology have taught us much about the structural origins of enzyme catalytic power and specificity, the field remains as vibrant as ever, with new questions to answer and new structures to deposit.

Truth sometimes triumphs: The history of structural enzymology

ACS Fall 2021

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