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1.
Previous studies from this laboratory have shown that the thermolysin fragment 121–316, comprising entirely the“all-α” COOH-terminal
structural domain 158–316, as well as fragment 206–316 (fragment FII) are able to refold into a native-like, stable structure
independently from the rest of the protein molecule. The present report describes conformational properties of fragments 228–316
and 255–316 obtained by chemical and enzymatic cleavage of fragment FII, respectively. These subfragments are able to acquire
a stable conformation of native-like characteristics, as judged by quantitative analysis of secondary structure from far-ultra-violet
circular dichroism spectra and immunochemical properties using rabbit anti-thermolysin antibodies. Melting curves of the secondary
structure of the fragments show cooperativity with a temperature of half-denaturationT
mof 65–66°C. The results of this study provide evidence that it is possible to isolate stable supersecondary structures (folding
units) of globular proteins and correlate well with predictions of subdomains of the COOH-terminal structural domain 158–316
of thermolysin. 相似文献
2.
Swire J 《Journal of molecular evolution》2007,64(5):558-571
Most investigations of the forces shaping protein evolution have focussed on protein function. However, cells are typically
50%–75% protein by dry weight, with protein expression levels distributed over five orders of magnitude. Cells may, therefore,
be under considerable selection pressure to incorporate amino acids that are cheap to synthesize into proteins that are highly
expressed. Such selection pressure has been demonstrated to alter amino acid usage in a few organisms, but whether “cost selection”
is a general phenomenon remains unknown. One reason for this is that reliable protein expression level data is not available
for most organisms. Accordingly, I have developed a new method for detecting cost selection. This method depends solely on
interprotein gradients in amino acid usage. Applying it to an analysis of 43 whole genomes from all three domains of life,
I show that selection on the synthesis cost of amino acids is a pervasive force in shaping the composition of proteins. Moreover,
some amino acids have different price tags for different organisms—the cost of amino acids is changed for organisms living
in hydrothermal vents compared with those living at the sea surface or for organisms that have difficulty acquiring elements
such as nitrogen compared with those that do not—so I also investigated whether differences between organisms in amino acid
usage might reflect differences in synthesis or acquisition costs. The results suggest that organisms evolve to alter amino
acid usage in response to environmental conditions.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
[Reviewing Editor: Hector Musto] 相似文献
3.
The production and analysis of individual structural domains is a common strategy for studying large or complex proteins, which may be experimentally intractable in their full-length form. However, identifying domain boundaries is challenging if there is little structural information concerning the protein target. One experimental procedure for mapping domains is to screen a library of random protein fragments for solubility, since truncation of a domain will typically expose hydrophobic groups, leading to poor fragment solubility. We have coupled fragment solubility screening with global data analysis to develop an effective method for identifying structural domains within a protein. A gene fragment library is generated using mechanical shearing, or by uracil doping of the gene and a uracil-specific enzymatic digest. A split green fluorescent protein (GFP) assay is used to screen the corresponding protein fragments for solubility when expressed in Escherichia coli. The soluble fragment data are then analyzed using two complementary approaches. Fragmentation “hotspots” indicate possible interdomain regions. Clustering algorithms are used to group related fragments, and concomitantly predict domain location. The effectiveness of this Domain Seeking procedure is demonstrated by application to the well-characterized human protein p85α. 相似文献
4.
In maturing seed cells, proteins that accumulate in the protein storage vacuoles (PSVs) are synthesized on the endoplasmic reticulum (ER) and transported by vesicles to the PSVs. Vacuolar sorting determinants (VSDs) which are usually amino acid sequences of short or moderate length direct the proteins to this pathway. VSDs identified so far are classified into two types: sequence specific VSDs (ssVSDs) and C-terminal VSDs (ctVSDs). We previously demonstrated that VSDs of α′ and β subunits of β-conglycinin, one of major storage proteins of soybean (Glycine max), reside in the C-terminal ten amino acids. Here we show that both types of VSDs coexist within this region of the α′ subunit. Although ctVSDs can function only at the very C-termini of proteins, the C-terminal ten amino acids of α′ subunit directed green fluorescent protein (GFP) to the PSVs even when they were placed at the N-terminus of GFP, indicating that an ssVSD resides in the sequence. By mutation analysis, it was found that the core sequence of the ssVSD is Ser-Ile-Leu (fifth to seventh residues counted from the C-terminus) which is conserved in the α and β subunits and some vicilin-like proteins. On the other hand, the sequence composed of the C-terminal three amino acids (AFY) directed GFP to the PSVs when it was placed at the C-terminus of GFP, though the function as a VSD was disrupted at the N-terminus of GFP, indicating that the AFY sequence is a ctVSD. 相似文献
5.
With yeast two-hybrid methods, we used a C-terminal fragment (residues 1697–2145) of non-erythroid beta spectrin (βII-C),
including the region involved in the association with alpha spectrin to form tetramers, as the bait to screen a human brain
cDNA library to identify proteins interacting with βII-C. We applied stringent selection steps to eliminate false positives
and identified 17 proteins that interacted with βII-C (IPβII-C s). The proteins include a fragment (residues 38–284) of “THAP domain containing, apoptosis associated protein 3, isoform
CRA g”, “glioma tumor suppressor candidate region gene 2” (residues 1-478), a fragment (residues 74–442) of septin 8 isoform
c, a fragment (residues 704–953) of “coatomer protein complex, subunit beta 1, a fragment (residues 146–614) of zinc-finger
protein 251, and a fragment (residues 284–435) of syntaxin binding protein 1. We used yeast three-hybrid system to determine
the effects of these βII-C interacting proteins as well as of 7 proteins previously identified to interact with the tetramerization
region of non-erythroid alpha spectrin (IPαII-N s) [1] on spectrin tetramer formation. The results showed that 3 IPβII-C s were able to bind βII-C even in the presence of αII-N, and 4 IPαII-N s were able to bind αII-N in the presence of βII-C. We also found that the syntaxin binding protein 1 fragment abolished
αII-N and βII-C interaction, suggesting that this protein may inhibit or regulate non-erythroid spectrin tetramer formation. 相似文献
6.
Protein–protein interactions (PPIs) play a central role in virtually all biological processes and have been the focus of intense
investigation from structural molecular biology to cell biology for the majority of the last two decades and, more recently,
are emerging as important targets for pharmaceutical intervention. A common motif found at the interface of PPIs is the α-helix,
suggesting that, in the same way as the “lock and key” model has evolved for competitive inhibition of enzymes, it should
be possible to elaborate “rule-based” approaches for inhibition of helix-mediated PPIs. This review will describe the biological
function and structural features of a series of representative helix-mediated PPIs and discuss approaches that are being developed
to target these interactions with small molecules that employ non-natural amino acids. 相似文献
7.
Summary. Amino acids are widely used in biotechnology applications. Since amino acids are natural compounds, they can be safely used
in pharmaceutical applications, e.g., as a solvent additive for protein purification and as an excipient for protein formulations.
At high concentrations, certain amino acids are found to raise intra-cellular osmotic pressure and adjust to the high salt
concentrations of the surrounding medium. They are called “compatible solutes”, since they do not affect macromolecular function.
Not only are they needed to increase the osmotic pressure, they are known to increase the stability of the proteins. Sucrose,
glycerol and certain amino acids were used to enhance the stability of unstable proteins after isolation from natural environments.
The mechanism of the action of these protein-stabilizing amino acids is relatively well understood. On the contrary, arginine
was accidentally discovered as a useful reagent for assisting in the refolding of recombinant proteins. This effect of arginine
was ascribed to its ability to suppress aggregation of the proteins during refolding, thereby increasing refolding efficiency.
By the same mechanism, arginine now finds much wider applications than previously anticipated in the research and development
of proteins, in particular in pharmaceutical applications. For example, arginine solubilizes proteins from loose inclusion
bodies, resulting in efficient production of active proteins. Arginine suppresses protein–protein interactions in solution
and also non-specific adsorption to gel permeation chromatography columns. Arginine facilitates elution of bound proteins
from various column resins, including Protein-A or dye affinity columns and hydrophobic interaction columns. This review covers
various biotechnology applications of amino acids, in particular arginine. 相似文献
8.
Summary We examine in this paper one of the expected consequences of the hypothesis that modern proteins evolved from random heteropeptide
sequences. Specifically, we investigate the lengthwise distributions of amino acids in a set of 1,789 protein sequences with
little sequence identity using the run test statistic (r
o) of Mood (1940,Ann. Math. Stat.
11, 367–392). The probability density ofr
o for a collection of random sequences has mean=0 and variance=1 [the N(0,1) distribution] and can be used to measure the tendency
of amino acids of a given type to cluster together in a sequence relative to that of a random sequence. We implement the run
test using binary representations of protein sequences in which the amino acids of interest are assigned a value of 1 and
all others a value of 0. We consider individual amino acids and sets of various combinations of them based upon hydrophobicity
(4 sets), charge (3 sets), volume (4 sets), and secondary structure propensity (3 sets). We find that any sequence chosen
randomly has a 90% or greater chance of having a lengthwise distribution of amino acids that is indistinguishable from the
random expectation regardless of amino acid type. We regard this as strong support for the random-origin hypothesis. However,
we do observe significant deviations from the random expectation as might be expected after billions years of evolution. Two
important global trends are found: (1) Amino acids with a strong α-helix propensity show a strong tendency to cluster whereas
those with β-sheet or reverse-turn propensity do not. (2) Clustered rather than evenly distributed patterns tend to be preferred
by the individual amino acids and this is particularly so for methionine. Finally, we consider the problem of reconciling
the random nature of protein sequences with structurally meaningful periodic “patterns” that can be detected by sliding-window,
autocorrelation, and Fourier analyses. Two examples, rhodopsin and bacteriorhodopsin, show that such patterns are a natural
feature of random sequences. 相似文献
9.
Jeffrey Tze-Fei Wong 《Origins of life and evolution of the biosphere》2007,37(4-5):403-408
The coevolution theory proposes that primordial proteins consisted only of those amino acids readily obtainable from the prebiotic
environment, representing about half the twenty encoded amino acids of today, and the missing amino acids entered the system
as the code expanded along with pathways of amino acid biosynthesis. The isolation of genetic code mutants, and the antiquity
of pretran synthesis revealed by the comparative genomics of tRNAs and aminoacyl-tRNA synthetases, have combined to provide
a rigorous proof of the four fundamental tenets of the theory, thus solving the riddle of the structure of the universal genetic
code.
Presented at: International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006. 相似文献
10.
Rafael Torres Martin de Rosales Marina Faiella Erik Farquhar Lawrence Que Jr Concetta Andreozzi Vincenzo Pavone Ornella Maglio Flavia Nastri Angela Lombardi 《Journal of biological inorganic chemistry》2010,15(5):717-728
The design, synthesis, and metal-binding properties of DF3, a new de novo designed di-iron protein model are described (“DF”
represents due ferri, Italian for “two iron,” “di-iron”). DF3 is the latest member of the DF family of synthetic proteins. They consist of helix–loop–helix
hairpins, designed to dimerize and form an antiparallel four-helix bundle that encompasses a metal-binding site similar to
those of non-heme carboxylate-bridged di-iron proteins. Unlike previous DF proteins, DF3 is highly soluble in water (up to
3 mM) and forms stable complexes with several metal ions (Zn, Co, and Mn), with the desired secondary structure and the expected
stoichiometry of two ions per protein. UV–vis studies of Co(II) and Fe(III) complexes confirm a metal-binding environment
similar to previous di-Co(II)- and di-Fe(III)-DF proteins, including the presence of a μ-oxo-di-Fe(III) unit. Interestingly,
UV–vis, EPR, and resonance Raman studies suggest the interaction of a tyrosine adjacent to the di-Fe(III) center. The design
of DF3 was aimed at increasing the accessibility of small molecules to the active site of the four-helix bundle. Indeed, binding
of azide to the di-Fe(III) site demonstrates a more accessible metal site compared with previous DFs. In fact, fitting of
the binding curve to the Hill equation allows us to quantify a 150% accessibility enhancement, with respect to DF2. All these
results represent a significant step towards the development of a functional synthetic DF metalloprotein. 相似文献
11.
Yoshihito Kitamura Satoshi Mori Wen Chen Jun Sumaoka Makoto Komiyama 《Journal of biological inorganic chemistry》2006,11(1):13-16
By using the recently developed man-made DNA cutter [a combination of Ce(IV)/EDTA and two DNA additives], green fluorescent
protein (GFP) was converted to closely related blue fluorescent protein (BFP). The phosphodiester linkages at T196-A200 in
the sense strand of GFP were hydrolyzed by the cutter, and the A1-T196 fragment in the product was selectively connected with
the downstream fragment (C197-A720) of BFP by T4 DNA ligase. This recombination changed three codons in the GFP gene (TGC
at 196–198, TAT at 199–201, and ACC at 502–504) to TCT, CAT, and ATC in BFP, and accordingly three amino acids in GFP (Cys65,
Tyr66, and Thr167) were altered to Ser65, His66, and Ile167. The recombinant gene was successfully expressed in Escherichia coli and emitted blue fluorescence, confirming the absence of undesired side reactions (mutation, deletion, insertion, depurination,
etc.) in the DNA manipulation.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
12.
To investigate the function of the N-terminal immunoglobulin (Ig)-like domain of the human interleukin-6 receptor α-chain (hIL-6R), we constructed a soluble human
interleukin-6 receptor (shIL-6R) (named EC05, amino acids 20–354) and soluble variants of the shIL-6R lacking the Ig-like
domain (named EC70, amino acids 105–354). The two extracellular portions of hIL-6R were expressed as soluble fusion proteins
with thioredoxin in Escherichia coli and purified by using Ni-NTA agarose. Western blot showed that purified proteins were immunoreactive with the antibody against
hIL-6R. They also possessed specific binding activity with human interleukin-6 (hIL-6) in ELISA analysis.
Jing Wang and Zhenhui Yang contributed equally to this work. 相似文献
13.
Two phytochromes, CphA and CphB, from the cyanobacterium Calothrix PCC7601, with similar size (768 and 766 amino acids) and domain structure, were investigated for the essential length of
their protein moiety required to maintain the spectral integrity. Both proteins fold into PAS-, GAF-, PHY-, and Histidine-kinase
(HK) domains. CphA binds a phycocyanobilin (PCB) chromophore at a “canonical” cysteine within the GAF domain, identically
as in plant phytochromes. CphB binds biliverdin IXα at cysteine24, positioned in the N-terminal PAS domain. The C-terminally
located HK and PHY domains, present in both proteins, were removed subsequently by introducing stop-codons at the corresponding
DNA positions. The spectral properties of the resulting proteins were investigated. The full-length proteins absorb at (CphA)
663 and 707 nm (red-, far red-absorbing P
r and P
fr forms of phytochromes) and at (CphB) 704 and 750 nm. Removal of the HK domains had no effect on the absorbance maxima of
the resulting PAS–GAF–PHY constructs (CphA: 663/707 nm, CphB: 704/750 nm, P
r/P
fr, respectively). Further deletion of the “PHY” domains caused a blue-shift of the P
r and P
fr absorption of CphA (λ
max: 658/698 nm) and increased the amount of unproperly folded apoprotein, seen by a reduced capability to bind the chromophore
in photoconvertible manner. In CphB, however, it practically impaired the formation of P
fr, i.e., showing a very low oscillator strength absorption band, whereas the P
r form remains unchanged (702 nm). This finding clearly indicates a different interaction between domains in the “typical”,
PCB binding and in the biliverdin-binding phytochromes, and demonstrates a loss of oscillator strength for the latter, most
probably due to a strong conformational distortion of the chromophore in the CphB P
fr form.
Proceedings of the XVIII Congress of the Italian Society of Pure and Applied Biophysics (SIBPA), Palermo, Sicily, September
2006. 相似文献
14.
Cristiano Chiarabelli Davide De Lucrezia 《Origins of life and evolution of the biosphere》2007,37(4-5):357-361
Starting from the statement that no reliable methods are known to produce high molecular weight polypeptides under prebiotic
conditions, a possible approach, at least to understand the differences between extant proteins and the possible large number
of never born proteins, could be biological. Using the phage display method a large library of totally random amino acidic
sequences was obtained. Consequently, different experiments to directly consider the frequency of stable folds were performed,
and the interesting results obtained from such new approach are discussed in terms of contingency, contributing to the discussion
on the selection mechanism of extant proteins.
Presented at the International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana”
Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006. 相似文献
15.
Hope E. Stansfield Bethany P. Kulczewski Kyle E. Lybrand Elizabeth R. Jamieson 《Journal of biological inorganic chemistry》2009,14(2):193-199
Protein microarrays have been used extensively to identify protein–protein interactions; however, this technology has not
been widely applied to protein–DNA interactions. In particular, this work demonstrates the utility of this technique for rapidly
identifying interactions of proteins with metal-modified DNA. Protein macroarray experiments were carried out with high mobility
group protein 1 (HMG-1) and cisplatin- and chromium-modified 50-mer oligonucleotides to demonstrate “proof of principle.”
Commercially available protein microarrays containing many different classes of human proteins were then employed to search
for additional interactions with cisplatin-modified DNA. The results of the microarray experiments confirmed some known interactions
and, more importantly, identified many novel protein interactions, demonstrating the utility of this method as a rapid, high-throughput
technique to discover proteins that interact with metal-modified DNA.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
16.
“Fairmount 1 thorny” (“FM1 thorny”) (a Rosa multiflora Thunb ex. J. Murr.) and a thornless sport of “FM1 thorny” (“Fairmount 1” (“FM1”)) were established in vitro to investigate
chimeral segregation under various levels of BA and to obtain a pure thornless rose. While the chimeral thornless sport was
expected to segregate in vitro and yield both thorny and thornless plantlets, “FM1 thorny” was to yield only thorny plants.
“FM1” segregated in vitro into its constituent genotypes and yielded thorny and thornless plantlets, suggesting that “FM1”
is chimeral. “FM1 thorny” produced only thorny plants in vitro. These results indicate that the “FM1 thorny” clone was not chimeral (pure thorny) and that the thornless regenerates of “FM1”
did not develop via somaclonal variation. There was a significant linear relationship between increasing BA concentration
and the percentage of thorny plants. Among a population of 690 tissue culture derived plants from all the BA experiments,
6 plants were classified as pure thornless plants 1 year later. 相似文献
17.
Joseph G. Major Jr. Melinda E. Wales John E. Houghton Julie A. Maley Jeffrey N. Davidson James R. Wild 《Journal of molecular evolution》1989,28(5):442-450
Summary Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) is the first unique enzyme common to de novo pyrimidine biosynthesis and
is involved in a variety of structural patterns in different organisms. InEscherichia coli, ATCase is a functionally independent, oligomeric enzyme; in hamster, it is part of a trifunctional protein complex, designated
CAD, that includes the preceding and subsequent enzymes of the biosynthetic pathway (carbamoyl phosphate synthetase and dihydroorotase).
The complete complementary DNA (cDNA) nucleotide sequence of the ATCase-encoding portion of the hamster CAD gene is reported
here. A comparison of the deduced amino acid sequences of the hamster andE. coli catalytic peptides revealed an overall 44% amino acid similarity, substantial conservation of predicted secondary structure,
and complete conservation of all the amino acids implicated in the active site of theE. coli enzyme. These observations led to the construction of a functional hybrid ATCase formed by intragenic fusion based on the
known tertiary structure of the bacterial enzyme. In this fusion, the amino terminal half (the “polar domain”) of the fusion
protein was provided by a hamster ATCase cDNA subclone, and the carboxyl terminal portion (the “equatorial domain”) was derived
from a clonedpyrBI operon ofE. coli K-12. The recombinant plasmid bearing the hybrid ATCase was shown to satisfy growth requirements of transformedE. coli pyrB
− cells. The functionality of thisE. coli-hamster hybrid enzyme confirms conservation of essential structure-function relationships between evolutionarily distant
and structurally divergent ATCases. 相似文献
18.
To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code,
numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze
the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases,
reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally
distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection “core”. Secondly,
a re-categorization of the amino acids according to their β-carbon stereochemistry, verified by charge density (at β-carbon)
calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro,
Val, Thr and Ala, remarkably overlapping the above “core”. These two lines of independent observations provide empirical arguments
for a contention that a seemingly “frozen” “core” could have formed at a certain evolutionary stage. The possible existence
of this codon “core” is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped
the code. Moreover, the genetic code listed in UCGA succession together with this codon “core” has recently facilitated an
identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code. 相似文献
19.
Li Y Efferson CL Ramesh R Peoples GE Hwu P Ioannides CG 《Cancer immunology, immunotherapy : CII》2011,60(4):515-524
Bacterial cell wall polysaccharides, such as PGN, bind and activate TLR-2, NOD2 and PGRP on monocytes/macrophages and activate
inflammation. We found that the peptides containing basic amino acids (cations) at N
-terminus and tyrosine at C-terminus interfered with activating ability of PGN. This finding is significant because the ECD
of TLR-2 in vivo encounters a large number of proteins or peptides. Some should bind ECD and “pre-form” TLR-2 to respond or
not to its activators, although they cannot activate TLR-2 alone. TLR-2 is receptor for a large number of ligands, including
lipopeptides and bacterial cell wall glycoproteins. A binding site for lipopeptides has been identified; however, a binding
site for soluble or multimeric PGN has not been proposed. To identify the candidate binding sites of peptides and PGN on TLR-2,
we modeled docking of peptides and of the PGN monomer (PGN-S-monomer) to extracellular domain (ECD-TLR-2) of the unbound TLR-2.
Quantification, in silico, of free energy of binding (DG) identified 2 close sites for peptides and PGN. The PGN-S-monomer
binding site is between amino acids TLR-2, 404–430 or more closely TLR-2, 417–428. The peptide-binding site is between amino
acids TLR-2, 434–455. Molecular models show PGN-S-monomer inserts its N
-acetyl-glucosamine (NAG) deep in the TLR-2 coil, while its terminal lysine interacts with inside (Glu403) and outside pocket (Tyr378). Peptides insert their two N
-terminal arginines or their C-terminal tyrosines in the TLR-2 coil. PGN did not bind the lipopeptide-binding site in the TLR-2.
It can bind the C-terminus, 572–586 (DG = 0.026 kcal), of “lipopeptide-bound” TLR-2. An additional, low-affinity PGN-binding
site is TLR-2 (227–237). MTP, MDP, and lysine-less PGN bind to TLR-2, 87–113. This is the first report identifying candidate
binding sites of monomer PGN and peptides on TLR-2. Experimental verification of our findings is needed to create synthetic
adjuvant for vaccines. Such synthetic PGN can direct both adjuvant and cancer antigen to TLR-2. 相似文献
20.
The amino acid composition of human alcohol dehydrogenase (ADH) was compared with alcohol dehydrogenases from different organisms
and with other proteins. Similar amino acid sequences in human ADH (template protein) and in other proteins were determined
by means of an original computer program. Analysis of amino acid motifs reveals that the ADHs from evolutionary more close
organisms have more common amino acid sequences. The quantity measure of amino acid similarity was the number of similar motifs
in analyzed protein per protein length. This value was measured for ADHs and for different proteins. For ADHs, this quotient
was higher than for proteins with different functions; for vertebrates it correlated with evolutionary closeness. The similar
operation of motif comparison was made with the help of program complex “MEME”. The analysis of ADHs revealed 4 motifs common
to 6 of 10 tested organisms and no such motifs for proteins of different function. The conclusion is that general amino composition
is more important for protein function than amino acid order and for enzymes of similar function it better correlates with
evolutionary distance between organisms. 相似文献