THE STRUCTURE OF PROTEINSTWO HYDROGEN-BONDED

HELICAL CONFIGURATIONS OF THE POL YPEPTIDE CHAIN (February 28 1951) JACS

Linus Carl Pauling, Robert B.Corey & H.R.BrasonThe Nobel Prize in Chemistry 1954

Presented by Yogesh Kumar

CSIR-CIMAP-JNU (Ph.D)

Protein Structures

All hydrogen bonds should be satisfied,i.e. distance N-O of about 2.7Å and anglebetween C = O and H – N less then ~30°

Distances and anglesBetween atoms

Determinants of helical structure

C-C=1.53Å , C==O = 1.23Å C-N=1.32ÅN-CR=1.47

Models satisfies all constraints

3.6 residues per turn

The number of residues per turn in Pauling's final model was 3.6. Today alpha helix is also known as (3.6 13 alpha ) helix . One helix contain 3.6 residues and 13 atoms

The helix with 5.1 residues per turn

The helix with 5.1 residues per turn.

The pi helix with 5.1 residues per turn--have yet to be found in nature and may not exist at all.

The α-helix – one of the two common structural elements in proteins

Completes one turn every 3.6 residues Rises ~5.4 Å with each turn Has hydrogen bonds between the C=O of residue i

and the N-H of residue i+4 Is right-handed

i

i+4

C

N

O

Complete one turn consist of 3.6 residues and each residue take 1.5 Å rise. So ( 1.5*3.6=5.5 Å.)

Why did Pauling and Corey succeed where others failed?

• The researchers who came up with earlier theories were crystallographers. • They were used to crystals in which everything is made up of integral

numbers," said Eisenberg. "Pauling was a broader, structural chemist--he was able to think outside the box.

• They did not consider only models with integer number of residues per turn!”• Understanding the importance of hydrogen bonds• Taking into account the planar peptide bond• Better knowledge of covalent bond lengths and angles

• Pauling and Corey's work was not without mistakes: research since the 1951 protein papers found the beta sheet to be twisted, not flat as suggested in Corey and Pauling's research.

• Since Pauling and Corey's famous series was first published, the ideas their explanation have proceeded from hypothesis to accepted fact to common knowledge.

• Dramatic verification of their work came in 1958, when the three-dimensional structure of myoglobin was found to be composed almost solely of alpha helices

Mistakes

Proof came 7 years later…

John Cowdery Kendrew The Nobel Prize in Chemistry 1962

Kendrew, J. C., Bodo, G., Dintzis, H. M. Parrish, R. G., Wyckoff, H., and Phillips, D. C. A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-ray Analysis. Nature, 181, 662 (1958).

Hierarchy of Protein Structure

Linear chain made of 20 possibleamino acids Alpha-helices, beta-sheets, turns

Motifs, domains

Oligomers, complexes

The Protein Data Bank (www.pdb.org)

Linus Pauling, Robert B.corey, and H. R. Branson* The structure of Proteins: Two Hydrogen-Bonded Helical Confirmations Of the polypeptide chain,.JACS, Vol37, 1951

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