Protein Structure and Function Lecture 2a: Introduction Enrico Purisima
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2-sheet handout
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Proteins as molecules • Structure ¾
Primary, secondary and tertiary
• Properties and function ¾
Structure giving rise to function
Cathepsin L
Proteins as molecules • Structure ¾
Primary, secondary and tertiary
• Properties and function ¾
Structure giving rise to function
Cathepsin L
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Proteins as molecules • Structure ¾
Primary, secondary and tertiary
• Properties and function ¾
Structure giving rise to function
Cathepsin L
Proteins as molecules • Structure ¾
Primary, secondary and tertiary
• Properties and function ¾
Structure giving rise to function
Cathepsin L
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Etymology of the word “protein” 1838 - Name given by Mulder to a complex residual nitrogenous substance, of tolerably constant composition, obtained from casein, fibrin, and egg albumin, to which he assigned the formula C40H62N10O12, and which he regarded as the essential constituent of organized bodies, animal or vegetable (obs.). [1838 MULDER in Bulletin des Sciences Phys. en Néerlande 111 La matière organique, étant un principe général de toutes les parties constituantes du corps animal..pourrait se nommer Protéine de proteios.] Source: Oxford English Dictionary
http://www.archive.org/details/bulletindesscien00leyd
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Bulletin des Sciences Phys. en Néerlande, 1838, p. 111
“Protein” 1844 DUNGLISON Med. Lex., Protein, a product of the decomposition of albumen, &c., by potassa. 1851 CARPENTER Man. Phys. (ed. 2) 9 Proteine and Gelatine are remarkable, not only for containing four elements, but for the very large number of atoms of these components which enter into the single compound atom of each. 1854 BUSHNAN in Orr's Circ. Sc. I. Org. Nat. 45 According to a view which has excited much attention, these three proximate elements [albumen, fibrine, and caseine] are merely slightly modified forms of the one proximate element, proteine. Mülder [is] the author of this view. 1868 HUXLEY Phys. Basis of Life in Fortn. Rev. Feb. (1869) 135 All forms of protoplasm..yet examined, contain the four elements carbon, hydrogen, oxygen, and nitrogen, in very complex union... To this complex combination, the nature of which has never been determined with exactness, the name of Protein has been applied. 1896 Allbutt's Syst. Med. I. 415 In many [foods] the amount of protein is too small. Ibid. 520 Of the true chemical character of the enzymes we are ignorant. They are probably proteins. 1907 Jrnl. Physiol. XXXV. Proc. 26 Jan. Rept. on Proteid Nomencl. p. xviii, The word Protein is recommended as the general name of the whole group... It is at present so used both in America and Germany.
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Timeline • 1806 – First amino acid isolated • 1833 – Diastase, first enzyme isolated in concentrated form (Anselme Payen). Converts starch to sugar. • 1890 – First protein crystallized, albumin • 1897 – Enzyme activity outside of a living cell confirmed (Buchner), fermentation using lysate of yeast cells • 1910 – Michaelis-Menten kinetics • 1926 – First enzyme crystallized (Summer), urease • 1936 – Five more enzymes crystallized; enzymes are proteins • 1946 – Amino acid composition of a chymotrypsin (Stein and Moore)
Timeline, continued • 1951 – α-helix and β-sheet structures proposed (Pauling and Corey) • 1955 – First amino acid sequence of a protein, bovine insulin (Sanger) • 1960 – First 3D structure of a protein. ¾
• • • • •
Myoglobin (Kendrew), Hemoglobin (Perutz)
1966 – First 3D structure of an enzyme, lysozyme. 1975 – Recombinant DNA, site-specific mutagenesis 1980s – Protein structure determination by NMR (Wuthrich) 1988 – First 3D structure of a membrane protein 2000 – 3D structure of the ribosome
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Chemical composition of bacterial and mammalian cells Percent Total Weight Component
E. Coli (bacterium)
Mammalian cell
H2O
70
70
Inorganic ions (Na+, K+ Mg2+, Ca2+, Cl–, etc.
1
1
Misc. small metabolites
3
3
Proteins
15
18
RNA
6
1.1
DNA
1
0.25
Phospholipids
2
3
Other lipids
–
2
Polysaccharides
2
2
Total cell volume
2 x 10-12 cm3
4 x 10-9 cm3
(From Molecular Biology of the Cell, Alberts et al.)
Roles of Proteins • • • • • • •
Enzyme catalysis Transport and storage Coordinated motion Mechanical support Immune protection Signal transduction Regulation
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Putting it in perspective
How big or small is a protein? 1x
Zoom 2 x 102 One dot on the perimeter of the coin
1x
E. Coli (1500-2000 nm)
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Zoom 2 x 104 20,000x
1x
E. Coli (1500-2000 nm)
Ribosome (25 nm)
Zoom 2 x 106
X1
Lipid bilayer
Hemoglobin (6.4 nm)
Ribosome (25 nm) Amino acid (0.8 nm)
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Zoom 1 x 106, penny
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