A reexamination of the propensities of amino acids towards a particular secondary structure: classification of amino acids based on their chemical structure

The correlation between the primary and secondary structures of proteins was analysed using a large data set from the Protein Data Bank. Clear preferences of amino acids towards certain secondary structures classify amino acids into four groups: α-helix preferrers, strand preferrers, turn and bend preferrers, and His and Cys (the latter two amino acids show no clear preference for any secondary structure). Amino acids in the same group have similar structural characteristics at their Cβ and Cγ atoms that predicts their preference for a particular secondary structure. All α-helix preferrers have neither polar heteroatoms on Cβ and Cγ atoms, nor branching or aromatic group on the Cβ atom. All strand preferrers have aromatic groups or branching groups on the Cβ atom. All turn and bend preferrers have a polar heteroatom on the Cβ or Cγ atoms or do not have a Cβ atom at all. These new rules could be helpful in making predictions about non-natural amino acids.

Unnatural amino acids as probes of protein structure and function

Nonsense suppression methodology, for incorporating unnatural amino acids into proteins, has enabled a wide range of studies into protein structure and function using both in vitro and in vivo translation systems. Although methodological challenges remain, scores of unnatural amino acids have been employed that include both subtle and dramatic variants of the natural set. A number of insights that would not have been possible using conventional site-directed mutagenesis have been gained.     

Clustering of amino acids for protein secondary structure prediction

Simple hidden Markov models are proposed for predicting secondary structure of a protein from its amino acid sequence. Since the length of protein conformation segments varies in a narrow range, we ignore the duration effect of length distribution, and focus on inclusion of short range correlations of residues and of conformation states in the models. Conformation-independent and -dependent amino acid coarse-graining schemes are designed for the models by means of proper mutual information. We compare models of different level of complexity, and establish a practical model with a high prediction accuracy.     

Differences in hydration structure near hydrophobic and hydrophilic amino acids.

We use molecular dynamics to simulate recent neutron scattering experiments on aqueous solutions of N-acetyl-leucine-amide and N-acetyl-glutamine-amide, and break down the total scattering function into contributions from solute-solute, solute-water, water-water, and intramolecular correlations. We show that the shift of the main diffraction peak to smaller angle that is observed for leucine, but not for glutamine, is attributable primarily to alterations in water-water correlations relative to bulk. The perturbation of the water hydrogen-bonded network extends roughly two solvation layers from the hydrophobic side chain surface, and is characterized by a distribution of hydrogen bonded ring sizes that are more planar and are dominated by pentagons in particular than those near the hydrophilic side chain. The different structural organization of water near the hydrophobic solute that gives rise to the inward shift in the main neutron diffraction peak under ambient conditions may also provide insight into the same directional shift for pure liquid water as it is cooled and supercooled.     

Conformational properties of streptokinase--secondary structure and localization of aromatic amino acids.

The conformational properties of streptokinase (Sk) have been assessed by several spectroscopic techniques. A solvent accessibility of about 70% of the 22 Tyr residues was found by u.v. perturbation spectroscopy. Fluorescence spectroscopy indicates also the surface localization of the single Trp 6 residue. Circular dichroism (c.d.), infrared (i.r.), and Raman spectra were analysed in order to estimate the contents of secondary structure elements of Sk. Values in the range of 14-23% alpha-helices, 38-46% beta-structures, 10-30% turns and 12-23% residual structures were found. The characteristics of the c.d. spectrum support the classification of Sk as an alpha + beta protein. Effects of temperature, pH, and denaturants were studied by c.d. spectroscopy, and on spin-labelled Sk, by e.p.r. spectroscopy. Structural effects were induced at temperatures above 40 degrees C, pH values below 3.0 and urea concentrations above 2 M. At temperatures above 70 degrees C, at pH 2.1, and at urea and Gu.HCl concentrations of 7 M and 5 M, respectively, no further structural changes are revealed in the spectra. At temperatures around 50 degrees C, at pH 3.0, and denaturant concentrations of about 1 M Gu.HCl and 1 M to 2 M urea, c.d. effects were observed in the near-u.v. region indicating an increase in the asymmetry for aromatic amino acids in comparison with the structure of Sk in low ionic strength buffers at neutral pH, 20 degrees C and in the absence of denaturants. These effects were most pronounced for the temperature dependence of the c.d. spectra. E.p.r. spectroscopy has shown that loosening of the protein surrounding of the spin label already begins at 1 M urea and that the mobility of the spin label points to a structural change in Sk at 46 degrees C.     

Synthesis and catalytic activity of polypeptides of regular structure containing polyfunctional amino acids

Synthesis and study of catalytic properties of a series of regular polypeptide which contain residues of polyfunctional amino acids forming the active centre of esterases are described viz. (Ala-Tyr-Glu)n, (His-Ser-Glu)n, (Glu-His-Glu)n, (His-Glu)n, (Ser-His-Glu)n, His-(Tyr-Glu)n. Possibility of constructing catalytically active model polypeptides which can substitute some hydrolytic enzymes is assessed. Monomers for polycondensation were been synthesized by carbodiimide method in solution, and polypeptides were obtained via 2,4,5-trichlorphenylates. Gel-filtration was used for fractionation of and molecular mass-determination of polypeptides. Catalytic properties of the synthetic polypeptides were studied in hydrolysis of p-NFA, Z-L-Ala-ONp, and Z-D-Ala-ONp. It was revealed that polypeptides (Ala-Tyr-Glu)n and (His-Ser-Glu)n possess, in hydrolysis of Z-L-Ala-ONp- and Z-D-Ala-ONp some enantioselectivity with the value of KD/KL 1.3 and 1.17, resp. The upper and lower limits of enantioselectivity as dependent of the molecular mass of the corresponding polypeptides have been determined.     

Some non-anomerically C-C-linked carbohydrate amino acids related to leucine-synthesis and structure determination

(5'R)-5'-Isobutyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione was synthesised starting from methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside via methyl 6-deoxy-6-isopropyl-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose applying the Bucherer-Bergs reaction. Its 5'-R configuration was confirmed by X-ray crystallography. Corresponding alpha-amino acid-methyl (5R)-5-amino-5-C-carboxy-5,6-dideoxy-6-isopropyl-alpha-D-lyxo-hexofuranoside (alternative name: 2-[methyl (4R)-beta-L-erythrofuranosid-4-C-yl]-D-leucine) was obtained from the above hydantoin by acid hydrolysis of the isopropylidene group followed by basic hydrolysis of the hydantoin ring. Analogous derivatives with 5S configuration, formed in a minority, were also isolated and characterised.     

系统比较氨基酸描述子在多肽定量构效关系中的应用

氨基酸描述子是采用多元统计方法从大量氨基酸性质参数中提取得到的少数关键信息成分,目前已被广泛应用于多肽生物活性预测及蛋白质功能判别等领域。鉴于近年来氨基酸描述子种类的极速扩增,收集了目前国内外发表的27种氨基酸描述子,并将其用于8组经典多肽集的结构表征及定量构效关系研究。通过系统比较这些描述子对同一肽集与不同肽集的统计建模结果,我们认为物理化学描述子的建模效果优于拓扑描述子,拓扑描述子的建模效果优于三维结构描述子,且已有诸多氨基酸描述子已经达到性能限度,如未考虑肽链内部各氨基酸残基的交互影响,肽配基与相应靶标蛋白的相互结合,因此不再建议按照传统思路进一步提出新型描述子种类。     

Transformation of some hydroxy amino acids to other amino acids

It has been observed that -hydroxy--amino acids are transformed into other amino acids, when heated in dilute solutions with phosphorous acid, phosphoric acid or their ammonium salts. It has been shown that as in the case of previously reported glycine-aldehyde reactions, glycine also reacts with acetone to give -hydroxyvaline under prebiologically feasible conditions. It is suggested, therefore, that the formation of -hydroxy--amino acids and their transformation to other amino acids may have been a pathway for the synthesis of amino acids under primitive earth conditions.     

Preparation and structure determination of two sugar amino acids via corresponding hydantoin derivatives

(4R)-2,3-O-Isopropylidene-methylspiro[4,6-dideoxy-alpha-L-lyxo+ ++-hexopyranosid-4,5'-imidazolidin]-2',4'-dione and (4R)-2,3-O-isopropylidene-methylspiro[4,6-dideoxy-beta-D-ribo-h exopyranosid-4,5'-imidazolidin]-2',4'-dione were prepared under various reaction conditions starting from methyl 6-deoxy-2,3-O-isopropylidene-alpha-L-lyxo-hexopyranosid-4-++ +ulose. Corresponding alpha-amino acids methyl (4R)-4-amino-4-C-carboxy-4,6-dideoxy-alpha-L-lyxo-hexopyranosid e and methyl (4R)-4-amino-4-C-carboxy-4,6-dideoxy-beta-D-ribo-hexopyranoside were obtained from the above hydantoins by selective acid hydrolysis of the isopropylidene group, followed by basic hydrolysis of the hydantoin ring. The crystal structures of both hydantoin derivatives are also presented.     

D-amino acids in the brain: structure and function of pyridoxal phosphate-dependent amino acid racemases

D-serine serves as a co-agonist of the N-methyl D-aspartate receptor in mammalian brains, and its behavior is probably related to neurological disorders such as schizophrenia, Alzheimer's disease and amyotrophic lateral sclerosis. D-Serine is synthesized by a pyridoxal 5'-phosphate (PLP)-dependent serine racemase. In this minireview, we provide a detailed discussion on the reaction mechanism of the PLP-dependent amino acid racemase on the basis of its 3D structure. We compared the eukaryotic serine racemase with bacterial alanine racemase, the best-studied enzyme among the PLP-dependent amino acid racemases, and thus suggested a putative reaction mechanism for mammalian D-serine synthesis.     

Stereoselective routes towards the synthesis of unusual bis(amino acids) and cyclic amino acids

Stereoselective syntheses are described of bridged bis(glycines) as conformationally constrained substitutes for cystine, and of cyclic -amino acids where the -carbon of the amino acid is part of a five-, six- or seven-membered ring which may hold a hydroxy group as a threonine analogue.     

Stereoselective routes towards the synthesis of unusual bis(amino acids) and cyclic amino acids

Summary Stereoselective syntheses are described of bridged bis(glycines) as conformationally constrained substitutes for cystine, and of cyclic α-amino acids where the α-carbon of the amino acid is part of a five-, six- or seven-membered ring which may hold a hydroxy group as a threonine analogue.