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1.
The definition of an Ecdysozoa clade among the protostomians, including all phyla with a regularly molted α-chitin-rich cuticle,
has been one of the most provocative hypotheses to arise from recent investigations on animal phylogeny. Here we present evidence
in favor of an arthropod-nematode clade, from the comparison of β-thymosin homologues among the Metazoa. Arthropods and nematodes
share the absence of the highly conserved β-thymosin form found in all other documented bilaterian phyla as well as sponges,
and the possession of a very unusual, internally triplicated homologue of the β-thymosin protein, unknown in other phyla.
We argue that such discrete molecular character is phylogenetically very powerful and provides strong evidence for the monophyly
of an arthropod-nematode clade.
Received: 17 December 1999 / Accepted: 7 July 2000 相似文献
2.
We conducted comprehensive sequence analysis of 5′ flanking regions of primate Alu elements. Information contents were computed and frequencies of 1024 pentanucleotides were measured to approximate the location
of a characteristic sequence and to specify its pattern(s), which may be involved in the integration of Alu elements into their host genomes. A large number of samples was used, the wide region of the 5′ end of Alu elements was analyzed, and comparisons were made among different subfamilies. Through our analyses, ``TTTTAAAAA' or ``(T)
m
(A)
n
' can be stated as a candidate for the characteristic sequence pattern, which resides around the region 5 to 20 base pairs
upstream of the 5′ end of Alu elements. This characteristic sequence pattern was more prominent in the sequences of younger Alus, which is a strong indication that the sequence pattern has a role at the time of Alu integration.
Received: 10 May 1999 / Accepted: 1 October 1999 相似文献
3.
The extracellular hemoglobins of cladocerans derive from the aggregation of 12 two-domain globin subunits that are apparently
encoded by four genes. This study establishes that at least some of these genes occur as a tandem array in both Daphnia magna and Daphnia exilis. The genes share a uniform structure; a bridge intron separates two globin domains which each include three exons and two
introns. Introns are small, averaging just 77 bp, but a longer sequence (2.2–3.2 kb) separates adjacent globin genes. A survey
of structural diversity in globin genes from other daphniids revealed three independent cases of intron loss, but exon lengths
were identical, excepting a 3-bp insertion in exon 5 of Simocephalus. Heterogeneity in the extent of nucleotide divergence was marked among exons, largely as a result of the pronounced diversification
of the terminal exon. This variation reflected, in part, varying exposure to concerted evolution. Conversion events were frequent
in exons 1–4 but were absent from exons 5 and 6. Because of this difference, the results of phylogenetic analyses were strongly
affected by the sequences employed in this construction. Phylogenies based on total nucleotide divergence in exons 1–4 revealed
affinities among all genes isolated from a single species, reflecting the impact of gene conversion events. In contrast, phylogenies
based on total nucleotide divergence in exons 5 and 6 revealed affinities among orthologous genes from different taxa.
Received: 8 March 1999 / Accepted: 14 July 1999 相似文献
4.
5.
To determine the origin and evolutionary significance of a recently discovered isoform of the estrogen receptor (ERβ), we
examined the phylogenetic relationship of ERβ to the well-known α isoform (ERα) and other steroid receptors. Our phylogenetic
analyses traced the origin of ERβ to a single duplication event at least 450 million years ago. Since this duplication, the
evolution of both ER isoforms has apparently been constrained such that 80% of the amino acid positions in the DNA binding
domain (DBD) and 53% of the ligand binding domain (LBD) have remained unchanged. Using the phylogenetic tree, we determined
the amount of evolutionary change that had occurred in two ER isoforms. The DBD and the LBD had lower rates of evolutionary
change compared to the NH2 terminal domain. However, even with strong selective constraints on the DBD and LBD, our phylogenetic analyses demonstrate
two clearly separate phylogenetic histories for ERα and ERβ dating back several hundred million years. The ancient duplication
of ER and the parallel evolution of the two ER isoforms suggest that, although ERα and ERβ share a substantial degree of sequence
identity, they play unique roles in vertebrate physiology and reproduction.
Received: 19 January 1999 / Accepted: 26 May 1999 相似文献
6.
Hiroyuki Satoh Naomi Inokuchi Yasuhiro Nagae Taro Okazaki 《Journal of molecular evolution》1999,49(1):122-129
The β-globin gene cluster of Wistar rat was extensively cloned and the embryonic genes were mapped and sequenced. Four overlapping
λ Dash recombinant clones cover about 31 kb and contain four nonadult β-globin genes, 5′–ε1–γ1–γ2–ψγ3–3′. The ε1 and γ2 are
active genes, since their protein products were detected in the fetal stage of the rat (Iwahara et al., J Biochem 119:360–366,
1996). The γ1 locus might be a pseudogene, since the ATA box in the promoter region is mutated to GTA; however, no other defect
is observed. The ψγ3 locus is a truncated pseudogene because a 19-base deletion, which causes a shift of the reading frame,
is observed between the second nucleotide of the putative codon 68 and codon 76. A sequence comparison suggests that the ψγ3
might be produced by a gene conversion event of the proto-γ-globin gene set. Possible histories of the evolution of rat nonadult
β-globin genes are discussed.
Received: 6 August 1998 / Accepted: 12 February 1999 相似文献
7.
Primary Structure and Phylogenetic Relationships of a Malate Dehydrogenase Gene from Giardia lamblia
The lactate and malate dehydrogenases comprise a complex protein superfamily with multiple enzyme homologues found in eubacteria,
archaebacteria, and eukaryotes. In this study we describe the sequence and phylogenetic relationships of a malate dehydrogenase
(MDH) gene from the amitochondriate diplomonad protist, Giardia lamblia. Parsimony, distance, and maximum-likelihood analyses of the MDH protein family solidly position G. lamblia MDH within a eukaryote cytosolic MDH clade, to the exclusion of chloroplast, mitochondrial, and peroxisomal homologues. Furthermore,
G. lamblia MDH is specifically related to a homologue from Trichomonas vaginalis. This MDH topology, together with published phylogenetic analyses of β-tubulin, chaperonin 60, valyl-tRNA synthetase, and
EF-1α, suggests a sister-group relationship between diplomonads and parabasalids. Since these amitochondriate lineages contain
genes encoding proteins which are characteristic of mitochondria and α-proteobacteria, their shared ancestry suggests that
mitochondrial properties were lost in the common ancestor of both groups.
Received: 14 September 1998 / Accepted: 29 December 1998 相似文献
8.
Albert Jeltsch 《Journal of molecular evolution》1999,49(1):161-164
Circular permutations of genes during molecular evolution often are regarded as elusive, although a simple model can explain
these rearrangements. The model assumes that first a gene duplication of the precursor gene occurs in such a way that both
genes become fused in frame, leading to a tandem protein. After generation of a new start codon within the 5′ part of the
tandem gene and a stop at an equivalent position in the 3′ part of the gene, a protein is encoded that represents a perfect
circular permutation of the precursor gene product. The model is illustrated here by the molecular evolution of adenine-N6 DNA methyltransferases. β- and γ-type enzymes of this family can be interconverted by a single circular permutation event.
Interestingly, tandem proteins, proposed as evolutionary intermediates during circular permutation, can be directly observed
in the case of adenine methyltransferases, because some enzymes belonging to type IIS, like the FokI methyltransferase, are built up by two fused enzymes, both of which are active independently of each other. The mechanism
for circular permutation illustrated here is very easy and applicable to every protein. Thus, circular permutation can be
regarded as a normal process in molecular evolution and a changed order of conserved amino acid motifs should not be interpreted
to argue against divergent evolution.
Received: 17 November 1998 / Accepted: 19 February 1999 相似文献
9.
Mariana Mondragón-Palomino Daniel Piñero Anne Nicholson-Weller Juan P. Laclette 《Journal of molecular evolution》1999,49(2):282-289
The plasma complement system comprises several activation pathways that share a common terminal route involving the assembly
of the terminal complement complex (TCC), formed by C5b–C9. The order of emergence of the homologous components of TCC (C6,
C7, C8α, C8β, and C9) has been determined by phylogenetic analyses of their amino acid sequences. Using all the sequence data
available for C6–C9 proteins, as well as for perforins, the results suggested that these TCC components originated from a
single ancestral gene and that C6 and C7 were the earliest to emerge. Our evidence supports the notion that the ancestral
gene had a complex modular composition. A series of gene duplications in combination with a tendency to lose modules resulted
in successive complement proteins with decreasing modular complexity. C9 and perforin apparently are the result of different
selective conditions to acquire pore-forming function. Thus C9 and perforin are examples of evolutionary parallelism.
Received: 16 August 1998 / Accepted: 12 March 1999 相似文献
10.
Mukhopadhyay D 《Journal of molecular evolution》2000,50(3):214-223
A serine protease inhibitor of the Kunitz-STI (soybean trypsin inhibitor) family, isolated from the legume seeds of winged
bean, was found to inhibit chymotrypsin at a 1:2 stoichiometric ratio. When the structure was determined in our laboratory,
it was found to form a characteristic β-trefoil fold, which is also seen in other proteins from distant families and sources.
The folding organization divides the protein into three approximately equal subdomains related by a pseudo-threefold axis
of symmetry passing parallel to the barrel axis of the trefoil. Following the now established idea that the present-day genes
originated from ancestral minigenes through evolution, the origin of the proteins having this β-trefoil organization is scrutinized
using its subdomain motif as the search probe. The results, based mainly on structural analyses, indicate the independent
existence of such a motif, mimicking the unknown ancestral protein(s) that might have been distributed in nature, not only
by gene duplication, but also by insertion and permutation in other folds. The understanding led to a hypothesis for the possible
origin of the Kunitz-STI family. On the basis of this model of evolution, structurally hypervariable regions were located
on the protein where mutations could be designed and a broad range of engineering of the protein's activity could be conceived.
Received: 20 January 1999 / Accepted: 6 October 1999 相似文献
11.
Benoit Cousineau Fabrice Leclerc Robert Cedergren 《Journal of molecular evolution》1997,45(6):661-670
Sequence similarity has given rise to the proposal that IF-2, EF-G, and EF-Tu are related through a common ancestor. We evaluate
this proposition and whether the relationship can be extended to other factors of protein synthesis. Analysis of amino acid
sequence similarity gives statistical support for an evolutionary affiliation among IF-1, IF-2, IF-3, EF-Tu, EF-Ts, and EF-G
and suggests further that this association is a result of gene duplication/fusion events. In support of this mechanism, the
three-dimensional structures of IF-3, EF-Tu, and EF-G display a predictable domain structure and overall conformational similarity.
The model that we propose consists of three consecutives duplication/fusion events which would have taken place before the
divergence of the three superkingdoms: eubacteria, archaea, and eukaryotes. The root of this protein superfamily tree would
be an ancestor of the modern IF-1 gene sequence. The repeated fundamental motif of this protein superfamily is a small RNA
binding domain composed of two α-helices packed along side of an antiparallel β-sheet.
Received: 17 October 1996 / Accepted: 10 June 1997 相似文献
12.
Arnason U Gullberg A Gretarsdottir S Ursing B Janke A 《Journal of molecular evolution》2000,50(6):569-578
Extant cetaceans are systematically divided into two suborders: Mysticeti (baleen whales) and Odontoceti (toothed whales).
In this study, we have sequenced the complete mitochondrial (mt) genome of an odontocete, the sperm whale (Physeter macrocephalus), and included it in phylogenetic analyses together with the previously sequenced complete mtDNAs of two mysticetes (the
fin and blue whales) and a number of other mammals, including five artiodactyls (the hippopotamus, cow, sheep, alpaca, and
pig). The most strongly supported cetartiodactyl relationship was: outgroup,((pig, alpaca),((cow, sheep),(hippopotamus,(sperm
whale,(baleen whales))))). As in previous analyses of complete mtDNAs, the sister-group relationship between the hippopotamus
and the whales received strong support, making both Artiodactyla and Suiformes (pigs, peccaries, and hippopotamuses) paraphyletic.
In addition, the analyses identified a sister-group relationship between Suina (the pig) and Tylopoda (the alpaca), although
this relationship was not strongly supported. The paleontological records of both mysticetes and odontocetes extend into the
Oligocene, suggesting that the mysticete and odontocete lineages diverged 32–34 million years before present (MYBP). Use of
this divergence date and the complete mtDNAs of the sperm whale and the two baleen whales allowed the establishment of a new
molecular reference, O/M-33, for dating other eutherian divergences. There was a general consistency between O/M-33 and the
two previously established eutherian references, A/C-60 and E/R-50. Cetacean (whale) origin, i.e., the divergence between
the hippopotamus and the cetaceans, was dated to ≈55 MYBP, while basal artiodactyl divergences were dated to ≥65 MYBP. Molecular
estimates of Tertiary eutherian divergences were consistent with the fossil record.
Received: 12 July 1999 / Accepted: 28 February 2000 相似文献
13.
The complete mitochondrial DNA (mtDNA) of the donkey and mtDNA comparisons among four closely related mammalian species-pairs 总被引:7,自引:0,他引:7
The nucleotide sequence of the complete mitochondrial genome of the donkey, Equus asinus, was determined. The length of the molecule is 16,670 bp. The length, however, is not absolute due to pronounced heteroplasmy
caused by variable numbers of two types of repetitive motifs in the control region. The sequence of the repeats is (a) 5′-CACACCCA
and (b) 5′-TGCGCGCA, respectively. The order of (a) and (b) can be expressed as {n[2(a)+(b)]+m(a)}. In 32 different clones analyzed the number of n and m ranged from 0 to 9 and 1 to 7. The two rRNA genes, the 13 peptide-coding genes, and the 22 tRNA genes of the donkey and the
horse, Equus caballus, were compared in detail. Total nucleotide difference outside the control region was 6.9%. Nucleotide difference between peptide-coding
genes ranged from 6.4% to 9.4% with a mean of 8.0%. In the inferred protein sequences of the 13 peptide-coding genes the amino
acid difference was 0.2–8.8%, and the mean for the 13 concatenated amino acid sequences was 1.9%. In the 22 tRNA genes, the
mean difference was 3.5%, and that in the two rRNA genes was 4.1%. The mtDNA differences between the donkey and the horse
suggest that the evolutionary separation of the two species occurred ≈9 million years ago. Analyses of differences among the
mtDNAs of three other species-pairs, harbor seal/grey seal, fin whale/blue whale, and Homo/common chimpanzee, showed that the relative evolutionary rate of individual peptide-coding genes varies among different species-pairs
and modes of comparison. The findings show that the superimposition of sequence data of one lineage for resolving and dating
evolutionary divergences of other lineages should be performed with caution unless based on comprehensive data.
Received: 15 October 1995 / Accepted: 15 April 1996 相似文献
14.
Briscoe AD 《Journal of molecular evolution》2000,51(2):110-121
It has been hypothesized that the UV-, blue-, and green-sensitive visual pigments of insects were present in the common ancestor
of crustaceans and insects, whereas red-sensitive visual pigments evolved later as a result of convergent evolution. This
hypothesis is examined with respect to the placement of six opsins from the swallowtail butterfly Papilio glaucus (PglRh1–6) in relationship to 46 other insect, crustacean, and chelicerate opsin sequences. All basal relationships established
with maximum parsimony analysis except two are present in the distance and maximum likelihood analyses. In all analyses, the
six P. glaucus opsins fall into three well-supported clades, comprised, respectively, of ultraviolet (UV), blue, and long-wavelength (LW)
pigments, which appear to predate the radiation of the insects. Lepidopteran green- and red-sensitive visual pigments form
a monophyletic clade, which lends support to the hypothesis from comparative physiological studies that red-sensitive visual
pigments in insects have paralogous origins. Polymorphic amino acid sites (180, 197, 277, 285, 308), which are essential for
generating the spectral diversity among the vertebrate red- and green-sensitive pigments are notably invariant in the Papilio red- and green-sensitive pigments. Other major tuning sites must be sought to explain the spectral diversification among
these and other insect visual pigments.
Received: 6 December 1999 / Accepted: 3 April 2000 相似文献
15.
The members of the PKA regulatory subunit family (PKA-R family) were analyzed by multiple sequence alignment and clustering
based on phylogenetic tree construction. According to the phylogenetic trees generated from multiple sequence alignment of
the complete sequences, the PKA-R family was divided into four subfamilies (types I to IV). Members of each subfamily were
exclusively from animals (types I and II), fungi (type III), and alveolates (type IV). Application of the same methodology
to the cAMP-binding domains, and subsequently to the region delimited by β-strands 6 and 7 of the crystal structures of bovine
RIα and rat RIIβ (the phosphate-binding cassette; PBC), proved that this highly conserved region was enough to classify unequivocally
the members of the PKA-R family. A single signature sequence, F–G–E–[LIV]–A–L–[LIMV]–x(3)–[PV]–R–[ANQV]–A, corresponding to
the PBC was identified which is characteristic of the PKA-R family and is sufficient to distinguish it from other members
of the cyclic nucleotide-binding protein superfamily. Specific determinants for the A and B domains of each R-subunit type
were also identified. Conserved residues defining the signature motif are important for interaction with cAMP or for positioning
the residues that directly interact with cAMP. Conversely, residues that define subfamilies or domain types are not conserved
and are mostly located on the loop that connects α-helix B′ and β strand 7.
Received: 2 November 2000/Accepted: 14 June 2001 相似文献
16.
The available amino acid sequences of the α-amylase family (glycosyl hydrolase family 13) were searched to identify their
domain B, a distinct domain that protrudes from the regular catalytic (β/α)8-barrel between the strand β3 and the helix α3. The isolated domain B sequences were inspected visually and also analyzed
by Hydrophobic Cluster Analysis (HCA) to find common features. Sequence analyses and inspection of the few available three-dimensional
structures suggest that the secondary structure of domain B varies with the enzyme specificity. Domain B in these different
forms, however, may still have evolved from a common ancestor. The largest number of different specificities was found in
the group with structural similarity to domain B from Bacillus cereus oligo-1,6-glucosidase that contains an α-helix succeeded by a three-stranded antiparallel β-sheet. These enzymes are α-glucosidase,
cyclomaltodextrinase, dextran glucosidase, trehalose-6-phosphate hydrolase, neopullulanase, and a few α-amylases. Domain B
of this type was observed also in some mammalian proteins involved in the transport of amino acids. These proteins show remarkable
similarity with (β/α)8-barrel elements throughout the entire sequence of enzymes from the oligo-1,6-glucosidase group. The transport proteins, in
turn, resemble the animal 4F2 heavy-chain cell surface antigens, for which the sequences either lack domain B or contain only
parts thereof. The similarities are compiled to indicate a possible route of domain evolution in the α-amylase family.
Received: 4 December 1996 / Accepted: 13 March 1997 相似文献
17.
Sun L Li Y McCullough AK Wood TG Lloyd RS Adams B Gurnon JR Van Etten JL 《Journal of molecular evolution》2000,50(1):82-92
Large dsDNA-containing chlorella viruses encode a pyrimidine dimer-specific glycosylase (PDG) that initiates repair of UV-induced
pyrimidine dimers. The PDG enzyme is a homologue of the bacteriophage T4-encoded endonuclease V. The pdg gene was cloned and sequenced from 42 chlorella viruses isolated over a 12-year period from diverse geographic regions. Surprisingly,
the pdg gene from 15 of these 42 viruses contain a 98-nucleotide intron that is 100% conserved among the viruses and another 4 viruses
contain an 81-nucleotide intron, in the same position, that is nearly 100% identical (one virus differed by one base). In
contrast, the nucleotides in the pdg coding regions (exons) from the intron-containing viruses are 84 to 100% identical. The introns in the pdg gene have 5′-AG/GTATGT and 3′-TTGCAG/AA splice site sequences which are characteristic of nuclear-located, spliceosomal processed
pre-mRNA introns. The 100% identity of the 98-nucleotide intron sequence in the 15 viruses and the near-perfect identity of
an 81-nucleotide intron sequence in another 4 viruses imply strong selective pressure to maintain the DNA sequence of the
intron when it is in the pdg gene. However, the ability of intron-plus and intron-minus viruses to repair UV-damaged DNA in the dark was nearly identical.
These findings contradict the widely accepted dogma that intron sequences are more variable than exon sequences.
Received: 13 May 1999 / Accepted: 20 August 1999 相似文献
18.
Ferritin, a protein widespread in nature, concentrates iron ∼1011–1012-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor
(based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin
gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants
but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals
and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization
in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning
of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals
but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the
absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In
plant ferritin genes, the number of introns (n= 7) is higher than in animals (n= 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin
gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary
protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin
genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding
sequences and the high conservation of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional
constraints may exist to maintain a particular intron/exon pattern within ferritin genes. In the case of plants, where ferritin
gene intron placement is unrelated to triplet codons or protein structure, and where ferritin is targeted to the plastid,
the selection pressure on gene organization may relate to RNA function and plastid/nuclear signaling.
Received: 25 July 1995 / Accepted: 3 October 1995 相似文献
19.
Emmanuel Mertens Uri S. Ladror Jennifer A. Lee Anya Miretsky Andrea Morris Catherine Rozario Robert G. Kemp Miklós Müller 《Journal of molecular evolution》1998,47(6):739-750
The pyrophosphate-dependent phosphofructokinase (PPi-PFK) of the amitochondriate protist Trichomonas vaginalis has been purified. The enzyme is a homotetramer of about 50 kDa subunits and is not subject to allosteric regulation. The
protein was fragmented and a number of peptides were sequenced. Based on this information a PCR product was obtained from
T. vaginalis gDNA and used to isolate corresponding cDNA and gDNA clones. Southern analysis indicated the presence of five genes. One
open reading frame (ORF) was completely sequenced and for two others the 5′ half of the gene was determined. The sequences
were highly similar. The complete ORF corresponded to a polypeptide of about 46 kDa. All the peptide sequences obtained were
present in the derived sequences. The complete ORF was highly similar to that of other PFKs, primarily in its amino-terminal
half. The T. vaginalis enzyme was most similar to PPi-PFK of the mitochondriate heterolobosean, Naegleria fowleri. Most of the residues shown or assumed to be involved in substrate binding in other PPi-PFKs were conserved in the T. vaginalis enzyme. Direct comparison and phylogenetic reconstruction revealed a significant divergence among PPi-PFKs and related enzymes, which can be assigned to at least four distantly related groups, three of which contain enzymes
of protists. The separation of these groups is supported with a high percentage of bootstrap proportions. The short T. vaginalis PFK shares a most recent common ancestor with the enzyme from N. fowleri. This pair is clearly separated from a group comprising the long (>60-kDa) enzymes from Giardia lamblia, Entamoeba histolytica pfk2, the spirochaetes Borrelia burgdorferi and Trepomena pallidum, as well as the α- and β-subunits of plant PPi-PFKs. The third group (``X') containing protist sequences includes the glycosomal ATP-PFK of Trypanosoma brucei, E. histolytica pfk1, and a second sequence from B. burgdorferi. The fourth group (``Y') comprises cyanobacterial and high-G + C, Gram-positive eubacterial sequences. The well-studied PPi-PFK of Propionibacterium freudenreichii is highly divergent and cannot be assigned to any of these groups. These four groups are well separated from typical ATP-PFKs,
the phylogenetic analysis of which confirmed relationships established earlier. These findings indicate a complex history
of a key step of glycolysis in protists with several early gene duplications and possible horizontal gene transfers.
Received: 5 December 1997 / Accepted: 18 March 1998 相似文献
20.
The ubiquitous glyoxalase system, which is composed of two enzymes, removes cellular cytotoxic methylglyoxal (MG). In an
effort to identify critical residues conserved in the evolution of the first enzyme in this system, glyoxalase I (GlxI), as
well as the structural implications of sequence alterations in this enzyme, a search of the National Center for Biotechnology
Information (NCBI) database of unfinished genomes was undertaken. Eleven putative GlxI sequences from pathogenic organisms
were identified and analyses of these sequences in relation to the known and previously identified GlxI enzymes were performed.
Several of these sequences show a very high similarity to the Escherichia coli GlxI sequence, most notably the 79% identity of the sequence identified from Yersinia pestis, the causative agent of bubonic plague. In addition to the conservation of residues critical to binding the catalytic metal
in all of the proposed GlxI enzymes, four regions in the Homo sapiens GlxI enzyme are absent in all of the bacterial GlxI sequences, with the exception of Pseudomonas putida. Removal of these regions may alter the active-site conformation of the bacterial enzymes in relation to that of the H. sapiens. These differences may be targeted for the development of inhibitors selective to the bacterial enzymes.
Received: 13 October 1999 / Accepted: 17 January 2000 相似文献