The anomalous hydrophilic character of proline

Gibbs, Paul R.; Radzicka, Anna; Wolfenden, Richard

doi:10.1021/ja00012a068

Cited by 40 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is a consequence of the proline structure, which excludes it from occupying internal positions in˛-helices andˇ-structures. 10 Proline also has been shown to alter fragmentation patterns in mass spectrometric (MS) Figure 1. Structure of the peptide used for analysis (N-CBZ-GlyPro-Gly-Gly-Pro-Ala).…”

Section: Introductionmentioning

confidence: 99%

Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation Fourier transform mass spectrometry and computational methodology

Tomlinson¹,

Scott²,

Wilkins³

et al. 1999

J. Mass Spectrom.

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation Fourier transform mass spectrometry and computational methodology

Tomlinson¹,

Scott²,

Wilkins³

et al. 1999

J. Mass Spectrom.

View full text Add to dashboard Cite

“…Opening ofthe ring and addition of the amide proton in the replacement of the proline residue is accounted for (AG = 0.49 kcal/mol) by using the difference in vapor to water distribution coefficients for N-acetylpyrrolidine and N-butylacetamide (25). The difference in hydration free energy between proline and serine is, therefore, estimated to be -6.6 kcal/mol.…”

mentioning

confidence: 99%

Evaluating the effects of a single amino acid substitution on both the native and denatured states of a protein.

Lin

Kim

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

For proteins that contain a disulfide bond, stability is linked thermodynamically to thiol-disulfide exchange. We use this relationship to obtain unfolding free energies for both the reduced and oxidized forms ofEscherichia coli thioredoxin from measurements of the effective concentrations of protein thiols. We then evaluate the effect of an amino acid substitution on disulfide bond formation in both the native and denatured states of the protein. Although the Pro-34 Ser substitution in thioredoxin results in a decrease of the effective concentration of protein thiols in the native state, the effective concentration increases in the denatured state. The net effect of the amino acid substitution is to increase the stability of reduced thioredoxin by -2.4 kcal/mol, whereas the stability of the oxidized protein remains the same. By assuming a two-state unfolding equilibrium and a mutation free energy of -7.7 kcal/mol for the Pro-34 -* Ser substitution in the reduced, urea-unfolded state (based on estimates of solvation and entropic changes), we obtain relative free energies for the native and denatured states of the mutant and wild-type proteins, in both the reduced and oxidized forms.The ratio between K1 and K2 can be obtained by measuring the effective concentration (Cuff) of the protein thiols in the native and unfolded states. Creighton introduced the concept of Ccff as a useful way to think about linkage relationships in protein stability (6). The Cuff of two interacting groups is the ratio of rate or equilibrium constants of otherwise identical intra-and intermolecular reactions (7). For a protein with two cysteines that can form a disulfide bond, Cuff can be obtained by comparing the pseudo equilibrium constant for disulfide bond formation in the protein (Kinta)

show abstract

“…Glycine is capable forming electrically neutral molecules as well as zwitterion types when at a moderately low pH while also being particularly soluble (Imamura et al, 1969;Shipman and Christoffersen, 1973). Proline having anomalous hydrophilic character can be rationalized as providing somewhat similar terms that would also advantage membrane transit of existing peptides (DeTar and Luthra, 1977;Gibbs et al, 1991;Prajapati et al, 2007). Using frequent combinations of either glycine or proline with other amino acids can be rationalized as creating peptides that present two electronic forms permissible for ready absorption.…”

Section: Conducting Absorptionmentioning

confidence: 99%

Gastric digestion of protein through pancreozyme action optimizes intestinal forms for absorption, mucin formation and villus integrity

Moran

2016

Animal Feed Science and Technology

View full text Add to dashboard Cite

a b s t r a c tRecovery of dietary protein proceeds through two phases of digestion before suitable forms exist for absorption. The first phase engages the gastric system where low pH weakens overall structures allowing pepsin to disrupt hydrophobic bonding and enhance aqueous compatibility. Secondly, trypsin, chymotrypsin and elastase proteolysis in conjunction with carboxypeptidases A and B cooperate to form a mixture of free amino acids and peptides that progressively arise in the small intestinal lumen. Free amino acids are dominated by the aromatic, aliphatic and basic ones while resulting peptides largely involve the nonessentials.Motility convectively transfers digestion products to the unstirred water layer of the upper villus where filtration limits entry to low molecular weight solutes that can be further digested by underlying enzymes to optimize membrane absorption. Mucin oligosaccharides are credited for creating a microenvironment having reduced pH's ∼5.5-6.0 that favors enzymes finalizing digestion as well as absorption of two type peptides. This pH is speculated to optimize peptide forms having either a zwitterion-like charge for proton gradient transfer or be non-dissociated and passively diffused. A high frequency of peptides having either glycine or proline can be rationalized as providing particularly favorable electronic terms for peptide absorption by either approach while being non-competitive.The upper villus has first access to absorbed products where goblet cells assure continuance of mucin and continuity of the unstirred water layer. Glutamine is their dominant nutrient for synthesis of mucin oligosaccharides while also providing glutamic acid for either formation of its associated protein or is consumed for energy. Dietary cystine and threonine are frequently limiting, and their assurance is necessary for the mucin core while ready availability of glycine and/or serine together with proline also foster mucin formation. Unused absorbed products descend the villus in venules adjacent to the surface and provide nutrition as well as information about the lumen for adaptation of replacement cells. Sustaining the villus with absorbed nutrients takes priority for continuation of operational efficiency before their entry into the portal system and subsequent body use.

show abstract

The anomalous hydrophilic character of proline

Cited by 40 publications

References 0 publications

Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation Fourier transform mass spectrometry and computational methodology

Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation Fourier transform mass spectrometry and computational methodology

Evaluating the effects of a single amino acid substitution on both the native and denatured states of a protein.

Gastric digestion of protein through pancreozyme action optimizes intestinal forms for absorption, mucin formation and villus integrity

Contact Info

Product

Resources

About