JMB celebrates 50 years of protein structure determination

In the September 11, 2009 issue (vol.392, issue 1) of JMB, there are a series of three articles on the determination of the first two protein structures (myoglobin and haemoglobin), an achievement accomplished by Perutz and Kendrew and their colleagues at the Cambridge MRC laboratory in 1950s. Of special interest of this series is the three authors — Bror Strandberg, Richard Dickerson and Michael Rossmann — leading scientists in structure biology, then postdocs actively involved in the late stage of the structure determination.

These reviews are vividly written and provide interesting background information and some technical details on X-ray crystal structure determination (especially on phase angle), and have the following titles:

1. "Building the Ground for the First Two Protein Structures: Myoglobin and Haemoglobin" by Bror Strandberg
2. "Myoglobin: A Whale of a Structure!" by Richard Dickerson
3. "Recollection of the Events Leading to the Discovery of the Structure of haemoglobin" by Michael Rossmann

With limited computing power and software support, protein structure determination was a difficult task at that time. Dickerson and Rossmann had to write their own programs to perform some calculations. However, the firsthand experience in both experiment and code development, on a significant project in a famous lab, may in part accounts for their success in structure biology.

I have known Dickerson's work on nucleic acid structures for a while, firstly through the famous Drew-Dickerson dodecamer (CGCGAATTCGCG), and I am intimately familiar with his NewHelix/FreeHelix programs. Nevertheless, it is only after reading his above article do I become aware of his initial protein experience. I like Dickerson's writing a lot. For example, on commenting the different styles of Kendrew and Perutz, he wrote: "John was the mentor, guide, and organizer. …… In contrast, Max was a hands-on bench biochemist whose center of gravity was always the laboratory itself. …… Both styles had their merits: one learned from John, but one learned with Max."

An interesting point from Rossmann's article is his description of a secret he kept to himself for many decades: "I [Rossmann] had been privileged to work on the haemoglobin project with Max, but it was also a project that Max had given his whole life to develop. In my enthusiasm to look at the results, I stole the final discovery from Max. …… With the realization of what I had done, all desire to explore further was completely gone." While I vaguely remembered this story from reading the book "Max Perutz and the Secret of Life" by Georgina Ferry several months ago, Rossmann's personal account would make it unforgettable.

It is worth noting that Perutz and Rossmann were among those few who initiated the PDB in 1971 at a Cold Spring Harbor meeting. Finally, given the expertise of the three authors, it is not surprising to read in the Epilogue that "Indeed, structural biology has become the unifying factor of just about every aspect of biology."