50 Years of Protein Structure Analysis
2009 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 392, no 1, 2-32 p.Article in journal (Refereed) Published
Fifty years ago, Max Perutz and John Kendrew at Cambridge University achieved something that many people at the time considered impossible: they were the first to use x-ray crystallography to decipher the molecular structures of proteins: haemoglobin and myoglobin. They found that both molecules were built from Linus Pauling's alpha helices, but folded and packed together in a complicated manner that never could have been deciphered by any other technique. With structure information in hand they could then explain how haemoglobin in the bloodstream binds and releases oxygen on cue, how it passes its cargo on to the related storage protein myoglobin, and how a single amino acid mutation can produce the catastrophe known as sickle-cell anemia. Perutz and Kendrew also observed that the folding of helices was identical in myoglobin and the two chains of haemoglobin, and this along with the simultaneously evolving new technique of amino acid sequence analysis established for the first time the concept of molecular evolution. The crystallographic puzzle was "cracked" by Perutz when he demonstrated that the binding of only two heavy metal atoms to horse haemoglobin changed the x-ray pattern enough to allow him to solve the "phase problem" and circumvent the main obstacle to protein crystal structure analysis. Because myoglobin has a single chain whereas haemoglobin has four, Kendrew's work with myoglobin progressed more rapidly; a low resolution structure appeared in 1956 and the high resolution structure in 1959. That same year saw the low resolution picture of haemoglobin, and the high resolution structure followed shortly thereafter. Much of the work in structure analysis was carried out by visiting postdoctoral fellows and technicians, under the watchful eye of Perutz and Kendrew. This celebratory review has been written by three of those former postdoctorals: Strandberg and Dickerson from the myoglobin project, and Rossmann from the haemoglobin.
Place, publisher, year, edition, pages
2009. Vol. 392, no 1, 2-32 p.
IdentifiersURN: urn:nbn:se:uu:diva-127516DOI: 10.1016/j.jmb.2009.05.087ISI: 000270123600002OAI: oai:DiVA.org:uu-127516DiVA: diva2:330524