An Amino Acid Substitution Matrix for Protein Conformation Identification

Amino acid substitution matrices play an essential role in protein sequence alignment, a fundamental task in bioinformatics. Most widely used matrices, such as PAM matrices derived from homologous sequences and BLOSUM matrices derived from aligned segments of PROSITE, did not integrate conformation information in their construction. There are a few structure-based matrices, which are derived from limited data of structure alignment. Using databases PDB_SELECT and DSSP, we create a database of sequence-conformation blocks which explicitly represent sequence-structure relationship. Members in a block are identical in conformation and are highly similar in sequence. From this block database, we derive a conformation-specific amino acid substitution matrix CBSM60. The matrix shows an improved performance in conformational segment search and homolog detection.

Substitution Matrices of Residue Triplets Derived from Protein Blocks.

In protein sequence alignment, residue similarity is usually evaluated by substitution matrix, which scores all possible exchanges of one amino acid with another. Several matrices are widely used in sequence alignment, including PAM matrices derived from homologous sequence and BLOSUM matrices derived from aligned segments of BLOCKS. However, most matrices have not addressed the high-order residue-residue interactions that are vital to the bioproperties of protein.With consideration for the inherent correlation in residue triplet, we present a new scoring scheme for sequence alignment. Protein sequence is treated as overlapping and successive 3-residue segments. Two edge residues of a triplet are clustered into hydrophobic or polar categories, respectively. Protein sequence is then rewritten into triplet sequence with 2 · 20 · 2 = 80 alphabets. Using a traditional approach, we construct a new scoring scheme named TLESUMhp (TripLEt SUbstitution Matrices with hydropobic and polar information) for pairwise substitution of triplets, which characterizes the similarity of residue triplets. The applications of this matrix led to marked improvements in multiple sequence alignment and in searching structurally alike residue segments. The reason for the occurrence of the ‘‘twilight zone,’’ i.e., structure explosion of lowidentity sequences, is also discussed.

Significant Residue Features Revealed By Eigenvalue Decomposition Analysis Of Blosum Matrices

Here we attempt to characterize protein evolution by residue features which dominate residue substitution in homologous proteins. Evolutionary information contained in residue substitution matrix is abstracted with the method of eigenvalue decomposition. Top eigenvectors in the eigenvalue spectrums are analyzed as function of the level of similarity, i.e. sequence identity (SI) between homologous proteins. It is found that hydrophobicity and volume are two significant residue features conserved in protein evolution. There is a transition point at SI approximate to 45%. Residue hydrophobicity is a feature governing residue substitution as SI >= 45%. Whereas below this SI level, residue volume is a dominant feature. (C) 2007 Elsevier B.V. All rights reserved.

Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel Deuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition.

Adaptive evolution of primate TRIM5 alpha, a gene restricting HIV-1 infection

Recent studies showed that nonhuman primate TRIM5 alpha can efficiently block HIV-1 infection in human cell lines. It can also restrict other retroviruses, therefore, suggested as a general defender against retrovirus infection. Here, we present an evolutionary analysis of TRIM5 alpha in primates. Our results demonstrated that TRIM5a has been evolving rapidly in primates, which is likely caused by Darwinian positive selection. The SPRY domain of TRM5 alpha, which may be responsible for recognition of incoming viral capsids showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5a ill primates might be an innate strategy developed in defending retrovirus infection during primate evolution. In addition, the comparative protein sequence analysis suggested that the amino acid substitution pattern at a single site (344R/Q/P) located in the SPRY domain may explain the differences in Susceptibilities of HIV-1 infection in diverse primate species. (c) 2005 Elsevier B.V. All rights reserved.

Episodic evolution of prolactin gene in primates

In the present study, we obtained exon 2-5 of prolactin (PRL) gene from four primate species by PCR and sequencing. Adding other genes available in GenBank, we calculate amino acid substitution rates for prolactin gene in primate. Comparison of nonsynonymous substitution rate to synonymous substitution rate ratios shows no evidence of positive selection for any lineage of primate prolactin gene. According to this and the facts that (i) no sites under positive selection are inferred by using maximum-likelihood method; (ii) among 32 amino acid replacement that occurred along the rapid evolutionary phase, only two are included in the 40 functionally important residues, indicating that amino acid replacement tends to occur in those functionally unimportant residues; (iii) partial of prolactin function is replaced by placental lactogen in primate at the rapid evolutionary phase of prolactin gene, we thus deem that it is relaxation of purifying selection to some extent rather than positive selection that enforces the rapid evolution of primate prolactin gene.

Evolutionary implications of avian infectious Bronchitis Virus (AIBV) analysis

For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus (AIBV) antigenic domain o

Molecular basis of transferrin polymorphism in goldfish (Carassius auratus)

Transferrin (TF) polymorphism was investigated in a color variety of goldfish (Carassius auratus), and its molecular basis analyzed. Three TF variants (A(1), A(2) and B-1) were identified from an inbred strain of the goldfish, of which A(1) and B-1 displayed a large electrophoretic difference on both native and SDS-PAGE gels. The TF cDNAs corresponding to variants A(1) and B-1 were cloned and sequenced from A(1)A(1), A(1)B(1) and B1B1 individuals, and their deduced amino acid sequences were analyzed. Substantial amino acid variation occurred between variants A(1) and B-1, with significant differences in peptide length, theoretical molecular weight (Mw) and isoelectric point (pI). No potential glycosylation sites were observed in the two amino acid sequences, which excluded the possibility that carbohydrate difference might cause electrophoretic variation among the TF variants. Further analysis suggested that the distinct electrophoretic mobility of the two variants A(1) and B-1 by SDS-PAGE resulted from their Mw difference, while the difference by the native PAGE could be explained by their pI variation. Furthermore, genomic DNA fragments containing the transferrin alleles were amplified and subjected to RFLP analysis in A(1)A(1), A(1)B(1) and B1B1 individuals. The data revealed characteristic banding patterns for each TF genotype, and demonstrated that the TF alleles A(1) and B-1 could be used as a co-dominant marker system. The initial work relating to the goldfish TF variants will benefit the understanding of the evolutionary and functional significance of TF polymorphism in fish.

CHEMICAL-IONIZATION MASS-SPECTROMETRY OF BENZOYL PEROXIDE - A RADICAL AROMATIC-SUBSTITUTION RESULTING IN BIPHENYLCARBOXYLIC ACID IN THE GAS-PHASE

A radical aromatic substitution resulting in biphenylcarboxylic acid is inferred for the decomposition of benzoyl peroxide from the chemical ionization and collision-induced dissociation mass spectra. The thermolysis of benzoyl peroxide gives rise to a benzoyloxy radical, which undergoes rapid decarboxylation and hydrogen abstraction leading to phenyl radical and benzoic acid, respectively. Attack of the resulting phenyl radical on the benzoic acid results in bipbenylcarboxylic acid. On the other hand, the phenyl radical abstracts a hydrogen atom to yield benzene, which is then subjected to the attack of a benzoyloxy radical, affording phenyl benzoate. This substitution reaction rather than the recombination of benzoyloxy and phenyl radicals is found to be responsible for the formation of phenyl benzoate under the present conditions.

Kinetics of acetic acid esterification with 2-ethoxyethanol over an Al-pillared clay catalyst

The Al-pillared clay catalyst obtained by exposing activated clay powder to sulfuric acid and aluminium salts and calcining in air at 373-673 K, was found to be highly active for the title reaction. The results indicated that pillared layer clay of the mixed oxide has been employed as parent catalysts for their definite structure and special properties which can be modified by the substitution of L and B acid sites cations. Solid acid catalyst of Supported aluminium was found to be highly active and selective at the 373-473 K temperature range for heterogeneous esterification. The activity is mainly attributed to the Lewis (and a considerably small number of Bronsted) acid sites whose number and strength increased due to pillaring. The water produced in the esterification can be induced by Al3+, which makes the catalyst surface to form strong B acid. Their acidities are obtained by pH measurement. If only B acid sites are > 70%, and pH < 1 in the 2-ethoxyethanol, there exists an activity of esterification. The used catalyst gave identical results with that of the fresh one. X-ray diffraction spectra show that the composition and active phase of the used catalysts are the same as the fresh ones. The kinetic study of the reaction was carried out by an integral method of analysis. The kinetic equation of surface esterification is y = 2.36x - 0.98.

Preparation and characterization of cationic corn starch with a high degree of substitution in dioxane-THF-water media

Cationic corn starch derivatives with a high degree of substitution are prepared in alkaline solution or in mixed media of organic solvent and water with different levels of the cationic reagent, 2,3-epoxypropyltrimethylammonium chloride. The starch cationization yield is investigated, and the results indicate that the degree of substitution (DS) of the samples depends on the reaction conditions and reaction media. The maximum DS values are up to 1.37 in 1,4-dioxane alkali ne-aqueous solution. Meanwhile, the structures of the cationic starch derivatives are characterized by elemental analyses, FTIR spectroscopy, X-ray diffraction, and C-13 NMR spectroscopy, as well as by SEM techniques.

Glycyrrhetinic acid-modified nanoparticles for drug delivery: Preparation and characterization

In this work, glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) used as liver targeted carrier for drug delivery, was prepared via hemisuccinate as a bridged group. The structure of the product was confirmed by IR and NMR methods and the degree of substitution (DS) of glycyrrhetinic acid groups was estimated via elemental analysis. Nanoparticles were formed by ionic gelation methold. The drug-loading and release behavior of the nanoparticles were investigated using BSA as the model drug. The results indicated that the carrier with a highest DS of 5.19% could be got and the DS was controlled by changing reaction temperature or feed ratio. BSA could be entrapped into the nanoparticles with the drug-loading ratio of 26.3% and the encapsulation efficiency of 81.5%. A sustained release over an 11-day period was observed in pH 7.4 in vitro.

Preparation of divalent rare earth ions in air by aliovalent substitution and spectroscopic properties of Ln(2+)

When alkaline earth ions in borates, phosphates or borophosphates [SrB4O7, SrB6O10, BaB8O13, MBPO5 (M=Ca,Sr)] are substituted partially and aliovalently by trivalent rare earth ions such as Sm3+, Eu3+, these rare earth ions can be reduced to divalent state by the produced negative charge vacancy V-M". The matrices must have appropriate structure containing a rigid three-dimensional network of tetragonal AO(4) groups (A=B,P). These groups can surround and isolate the produced divalent RE2+ ions from the reaction with oxygen. Therefore, this reduction reaction can be carried out even in air at high temperature. The produced divalent rare earth ions can be detected by luminescence and XANES methods and their spectroscopic properties are discussed.

Preparation of a composite film electrode containing 12-tungstosilicic acid and its electrocatalytic reduction for nitrite

A novel organic-inorganic composite film was formed by attaching Keegin-type heteropolyanion, SiW12O404- (devoted briefly as SiW12), on a glassy carbon electrode derivatized by 4-aminophenyl group. The composite film has an ionic bonding character between SiW12 and the surface amino group, which greatly improves the Blm stability and exhibits a more reversible electrochemical behavior. The modified electrode offers an excellent and stable electrocatalytic response for the reduction of nitrite. Possible mechanism was provided for the reaction of nitrite with SiW12O404-/aminophenyl composite film.