Franz Hofmeister 5265613 215691651 2008-05-29T08:13:58Z DOI bot 6652755 Citation maintenance. Initiated by [[User:Tarun2k|Tarun2k]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Franz Hofmeister''' (1850-1922) was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of [[protein]]s. Hofmeister was the first to propose that polypeptides were [[amino acid]]s linked by [[peptide bond]]s in 1902, although this model of protein [[primary structure]] was independently and simultaneously conceived by [[Emil Fischer]]. ==Early life== Hofmeister's father was a doctor in Prague, where Hofmeister first began his studies, under the physiologist Hugo Huppert, himself a student of Carl Lehmann. Hofmeister's ''Habilitationsschrift'' in 1879 concerned the peptic products of digestion. Hofmeister became professor of Pharmacology in Prague in 1885, then moved to Strassbourg in 1896. ==The Hofmeister series== {{main|Hofmeister series}} Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their [[secondary structure|secondary]] and [[tertiary structure]]. Anions appear to have a larger effect than cations, and are usually ordered :<math> \mathrm{F^{-} \approx SO_{4}^{2-} > HPO_{4}^{2-} > acetate > Cl^{-} > NO_{3}^{-} > Br^{-} > ClO_{3}^{-} > I^{-} > ClO_{4}^{-} > SCN^{-}} </math> (This is a partial listing; many more salts have been studied.) The order of cations is usually given as :<math> \mathrm{NH_{4}^{+} > K^{+} > Na^{+} > Li^{+} > Mg^{2+} > Ca^{2+} > guanidinium} </math> The mechanism of the Hofmeister series is not entirely clear, but seems to result mainly from effects on the solvent at higher salt concentrations (>100 mM). Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salt out"); in effect, they ''strengthen'' the [[hydrophobic interaction]]. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salt in") and decrease the order in water; in effect, they ''weaken'' the [[hydrophobic effect]]. However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to [[ribonuclease A]]). Ions that have a strong 'salting in' effect such as I<sup>-</sup> and SCN<sup>-</sup> are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they 'pull' the unfolding reaction.<ref name="baldwin">{{cite journal |author=Baldwin RL. |title=How Hofmeister ion interactions affect protein stability |journal=Biophys J |volume=71 |issue=4 |pages=2056–63 |year=1996 |pmid=8889180}}</ref> Moreover, they may have direct interactions with some standard hydrophobic molecules, e.g., [[benzene]]. ==Protein purification== The importance of the Hofmeister series to early protein work cannot be underestimated, since it provided the chief tool for purifying proteins (sulfate precipitation) over the next ~50 years, one that is still in use today. Hofmeister himself may have been the first to crystallize a protein, hen egg-white albumin. Repeated crystallization was a favorite purification technique in the early days of protein science, and was essential for its development. ==Proposal of protein primary structure== Hofmeister argued for peptide bonds by process of elimination. C-C, ether and ester bonds were unlikely considering the digestion by [[trypsin]]. =C-N-C= bonds could be eliminated because it would imply a much larger number of [[carboxylate]] groups than is observed experimentally. Hofmeister also argued for peptide bonds based on the [[biuret reaction]] observed with all proteins but never with free amino acids. Since [[biuret]] has the formula NH2-CO-NH-CO-NH2, that suggested the presence of similar peptide bonds in proteins. ==See also== * [[primary structure]] * [[peptide bond]] ==References== <references/> * Hofmeister F. (1888) ''Arch. Exptl. Pathol. Pharmakol.'', '''24''', 247. * Zhang Y and Cremer PS. (2006) ''Curr. Opin, Chem. Biol.'', '''10''' (6), 658-63. PMID 17035073 * Zhou HX. (2005) ''Proteins'', '''61''' (1), 69-78. PMID 16044460 * Tanford C and Reynolds J. (2001) ''Nature's robots: a history of proteins'', Oxford University Press. ISBN 0-19-850466-7 * Creighton TE. (1993) ''Proteins'', 2nd ed., W. H. Freeman. ISBN 0-7167-2317-4 * Jencks WP. (1969) ''Catalysis in Chemistry and Enzymology'', Dover republication (1987). ISBN 0-486-65460-5 * Collins KD.; Washabaugh MW. (1985) The Hofmeister effect and the behaviour of water at interfaces ''Q Rev Biophys'' '''18''' (4) PMID 3916340 [[Category:Biochemists|Hofmeister, Franz]] [[Category:German chemists|Hofmeister, Franz]] [[Category:1850 births|Hofmeister, Franz]] [[Category:1922 deaths|Hofmeister, Franz]] [[de:Franz Hofmeister]]