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1.
Nature's strategies for evolving catalytic functions can be deciphered from the information contained in the rapidly expanding protein sequence databases. However, the functions of many proteins in the protein sequence and structure databases are either uncertain (too divergent to assign function based on homology) or unknown (no homologs), thereby limiting the utility of the databases. The mechanistically diverse enolase superfamily is a paradigm for understanding the structural bases for evolution of enzymatic function. We describe strategies for assigning functions to members of the enolase superfamily that should be applicable to other superfamilies. 相似文献
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Enzymes of the thiolase superfamily catalyze the formation of carbon-carbon bond via the Claisen condensation reaction. Thiolases catalyze the reversible non-decarboxylative condensation of acetoacetyl-CoA from two molecules of acetyl-CoA, and possess a conserved Cys-His catalytic diad. Elongation enzymes (beta-ketoacyl-acyl carrier protein synthase (KAS) I and KAS II and the condensing domain of polyketide synthase) have invariant Cys and two His residues (CHH triad), while a Cys-His-Asn (CHN) triad is found in initiation enzymes (KAS III, 3-ketoacyl-CoA synthase (KCS) and the chalcone synthase (CHS) family). These enzymes all catalyze decarboxylative condensation reactions. 3-Hydroxyl-3-methylglutaryl-CoA synthase (HMGS) also contains the CHN triad, although it catalyzes a non-decarboxylative condensation. That the enzymes of the thiolase superfamily share overall similarity in protein structure and function suggested a common evolutionary origin. All thiolases were found to have, in addition to the Cys-His diad, either Asn or His (thus C(N/H)H) at a position corresponding to the His in the CHH and CHN triads. In our phylogenetic analyses, the thiolase superfamily was divided into four main clusters according to active site architecture. During the functional divergence of the superfamily, the active architecture was suggested to evolve from the C(H)H in archaeal thiolases to the C(N/H)H in non-archaeal thiolases, and subsequently to the CHH in the elongation enzymes and the CHN in the initiation enzymes. Based on these observations and available biochemical and structural evidences, a plausible evolutionary history for the thiolase superfamily is proposed that includes the emergence of decarboxylative condensing enzymes accompanied by a recruitment of the His in the CHH and CHN triads for a catalytic role during decarboxylative condensation. In addition, phylogenetic analysis of the plant CHS family showed separate clustering of CHS and non-CHS members of the family with a few exceptions, suggesting repeated gene birth-and-death and re-invention of non-CHS functions throughout the evolution of angiosperms. Based on these observations, predictions on the enzymatic functions are made for several members of the CHS family whose functions are yet to be characterized. Further, a moss CHS-like enzyme that is functionally similar to a cyanobacterial enzyme was identified as the most recent common ancestor to the plant CHS family. 相似文献
5.
Extracellular matrix degradation via enolase/plasminogen interaction: Evidence for a mechanism conserved in Metazoa
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Gerarda Grossi Annalisa Grimaldi Rosa A. Cardone Magnus Monné Stephan J. Reshkin Rossana Girardello Maria R. Greco Elena Coviello Simona Laurino Patrizia Falabella 《Biology of the cell / under the auspices of the European Cell Biology Organization》2016,108(6):161-178
6.
Analysis of the haloalkanoate dehalogenase superfamily (HADSF) has uncovered homologues occurring within the same organism that are found to possess broad, overlapping substrate specificities, and low catalytic efficiencies. Here we compare the HADSF phosphatase BT1666 from Bacteroides thetaiotaomicron VPI‐5482 to a homologue with high sequence identity (40%) from the same organism BT4131, a known hexose‐phosphate phosphatase. The goal is to find whether these enzymes represent duplicated versus paralogous activities. The X‐ray crystal structure of BT1666 was determined to 1.82 Å resolution. Superposition of the BT1666 and BT4131 structures revealed a conserved fold and identical active sites suggestive of a common physiological substrate. The steady‐state kinetic constants for BT1666 were determined for a diverse panel of phosphorylated metabolites to define its substrate specificity profile and overall level of catalytic efficiency. Whereas BT1666 and BT4131 are both promiscuous, their substrate specificity profiles are distinct. The catalytic efficiency of BT1666 (kcat/Km = 4.4 × 102M?1 s?1 for the best substrate fructose 1,6‐(bis)phosphate) is an order of magnitude less than that of BT4131 (kcat/Km = 6.7 × 103M?1 s?1 for 2‐deoxyglucose 6‐phosphate). The seemingly identical active‐site structures point to sequence variation outside the active site causing differences in conformational dynamics or subtle catalytic positioning effects that drive the divergence in catalytic efficiency and selectivity. The overlapping substrate profiles may be understood in terms of differential regulation of expression of the two enzymes or a conferred advantage in metabolic housekeeping functions by having a larger range of possible metabolites as substrates. Proteins 2011;. © 2011 Wiley‐Liss, Inc. 相似文献
7.
The DJ-1 superfamily (DJ-1/ThiJ/PfpI superfamily) is distributed across all three kingdoms of life. These proteins are involved
in a highly diverse range of cellular functions, including chaperone and protease activity. DJ-1 proteins usually form dimers
or hexamers in vivo and show at least four different binding orientations via distinct interface patches. Abnormal oligomerization of human DJ-1 is related to neurodegenerative disorders including Parkinson’s
disease, suggesting important functional roles of quaternary structures. However, the quaternary structures of the DJ-1 superfamily
have not been extensively studied. Here, we focus on the diverse oligomerization modes among the DJ-1 superfamily proteins
and investigate the functional roles of quaternary structures both computationally and experimentally. The oligomerization
modes are classified into 4 types (DJ-1, YhbO, Hsp, and YDR types) depending on the distinct interface patches (I-IV) upon
dimerization. A unique, rotated interface via patch I is reported, which may potentially be related to higher order oligomerization.
In general, the groups based on sequence similarity are consistent with the quaternary structural classes, but their biochemical
functions cannot be directly inferred using sequence information alone. The observed phyletic pattern suggests the dynamic
nature of quaternary structures in the course of evolution. The amino acid residues at the interfaces tend to show lower mutation
rates than those of non-interfacial surfaces. 相似文献
8.
Comparison of the complete human genome sequence to one of its closest relatives, the chimpanzee genome, provides a unique opportunity for exploring recent evolutionary events affecting the microsatellites in these species. A simple assumption on microsatellite distribution is that the total length of perfect repeats is constant compared to that of imperfect ones regardless of the repeat sequence. In this paper, we show that this is valid for most of the chimpanzee genome but not for a number of human chromosomes. Our results suggest accelerated evolution of microsatellites in the human genome relative to the chimpanzee lineage. 相似文献
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The use of the soil fumigant Telone II, which contains a mixture of cis- and trans-1,3-dichloropropene, to control plant-parasitic nematodes is a common agricultural practice for maximizing yields of various crops. The effectiveness of Telone II is limited by the rapid turnover of the dichloropropenes in the soil due to the presence of bacterial catabolic pathways, which may be of recent origin. The characterization of three enzymes in these pathways, trans-3-chloroacrylic acid dehalogenase (CaaD), cis-3-chloroacrylic acid dehalogenase (cis-CaaD), and malonate semialdehyde decarboxylase (MSAD), has uncovered intriguing catalytic mechanisms as well as a fascinating evolutionary lineage for these proteins. Sequence comparisons and mutagenesis studies revealed that all three enzymes belong to the tautomerase superfamily. Tautomerase superfamily members with known structures are characterized by a β-α-β structural fold. Moreover, they have a conserved N-terminal proline, which plays an important catalytic role. Mechanistic, NMR, and pH rate studies of the two dehalogenases, coupled with a crystal structure of CaaD inactivated by 3-bromopropiolate, indicate that they use a general acid/base mechanism to catalyze the conversion of their respective isomer of 3-chloroacrylate to malonate semialdehyde. The reaction is initiated by the conjugate addition of water to the C-2, C-3 double bond and is followed by the loss of HCl. MSAD processes malonate semialdehyde to acetaldehyde, and is the first identified decarboxylase in the tautomerase superfamily. The catalytic mechanism is not well defined but the N-terminal proline plays a prominent role and may function as a general acid catalyst, similar to its role in CaaD and cis-CaaD. These are the first structural and mechanistic details for tautomerase superfamily members that catalyze either a hydration or a decarboxylation reaction, rather than a tautomerization reaction, in which Pro-1 serves as a general acid catalyst rather than as a general base catalyst. The available information on the 1,3-dichloropropene catabolic enzymes allows speculation on the possible evolutionary origins of their activities. 相似文献
10.
Chao Liu Huan-Huan Chen Li-Zhou Tang Phyo Kay Khine Li-Hong Han Yu Song Yun-Hong Tan 《Plant Diversity》2022,44(4):377
Litsea, a non-monophyletic group of the tribe Laureae (Lauraceae), plays important roles in the tropical and subtropical forests of Asia, Australia, Central and North America, and the islands of the Pacific. However, intergeneric relationships between Litsea and Laurus, Lindera, Parasassafras and Sinosassafras of the tribe Laureae remain unresolved. In this study, we present phylogenetic analyses of seven newly sequenced Litsea plastomes, together with 47 Laureae plastomes obtained from public databases, representing six genera of the Laureae. Our results highlight two highly supported monophyletic groups of Litsea taxa. One is composed of 16 Litsea taxa and two Lindera taxa. The 18 plastomes of these taxa were further compared for their gene structure, codon usage, contraction and expansion of inverted repeats, sequence repeats, divergence hotspots, and gene evolution. The complete plastome size of newly sequenced taxa varied between 152,377 bp (Litsea auriculata) and 154,117 bp (Litsea pierrei). Seven of the 16 Litsea plastomes have a pair of insertions in the IRa (trnL-trnH) and IRb (ycf2) regions. The 18 plastomes of Litsea and Lindera taxa exhibit similar gene features, codon usage, oligonucleotide repeats, and inverted repeat dynamics. The codons with the highest frequency among these taxa favored A/T endings and each of these plastomes had nine divergence hotspots, which are located in the same regions. We also identified six protein coding genes (accD, ndhJ, rbcL, rpoC2, ycf1 and ycf2) under positive selection in Litsea; these genes may play important roles in adaptation of Litsea species to various environments. 相似文献
11.
Apoptosis and inflammation are important cellular processes that are highly regulated through specific protein-protein interactions (PPI). Proteins involved in these signaling cascades often carry PPI domains that belong to the death-domain superfamily. This includes the structurally well-characterized Death Domain (DD), the Death Effector Domain (DED) and the Caspase Recruitment Domain (CARD) subfamilies. Recently, a fourth member of the DD superfamily was identified, the Pyrin Domain (PYD). Based on sequence alignments, homology to other domains occurring in death-signalling pathways, and secondary-structure prediction, the PYD was predicted to have an overall fold similar to other DD superfamily members. Just recently, NMR structures of two PYDs have been determined. The PYD structures not only revealed the DD superfamily fold as previously predicted, but also distinct features that are characteristic exclusively for this subfamily. This review summarizes recent findings and developments regarding structural aspects of the DD superfamily, with a special emphasis on the PPIs of the DD superfamily. 相似文献
12.
Couture JF Legrand P Cantin L Labrie F Luu-The V Breton R 《Journal of molecular biology》2004,339(1):89-102
The aldo-keto reductase rabbit 20alpha-hydroxysteroid dehydrogenase (rb20alpha-HSD; AKR1C5) is less selective than other HSDs, since it exerts its activity both on androgens (C19 steroids) and progestins (C21 steroids). In order to identify the molecular determinants responsible for this reduced selectivity, binary (NADPH) and ternary (NADP(+)/testosterone) complex structures were solved to 1.32A and 2.08A resolution, respectively. Inspection of the cofactor-binding cavity led to the identification of a new interaction between side-chains of residues His222 and Lys270, which cover the central phosphate chain of the cofactor, reminiscent of the "safety-belt" found in other aldo-keto reductases. Testosterone is stabilized by a phenol/benzene tunnel composed of side-chains of numerous residues, among which Phe54, which forces the steroid to take up an orientation markedly contrasting with that found in HSD ternary complexes reported. Combining structural, site-directed mutagenesis, kinetic and fluorescence titration studies, we found that the selectivity of rb20alpha-HSD is mediated by (i) the relaxation of loop B (residues 223-230), partly controlled by the nature of residue 230, (ii) the nature of the residue found at position 54, and (iii) the residues found in the C-terminal tail of the protein especially the side-chain of the amino acid 306. 相似文献
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Claudia Alvarez‐Carreño Vikram Alva Arturo Becerra Antonio Lazcano 《Protein science : a publication of the Protein Society》2018,27(4):848-860
Hemerythrin‐like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear nonheme iron centers. However, in recent years, it has become increasingly evident that some members of the hemerythrin‐like superfamily also participate in many other biological processes. For instance, the binuclear nonheme iron site of YtfE, a hemerythrin‐like protein involved in the repair of iron centers in Escherichia coli, catalyzes the reduction of nitric oxide to nitrous oxide, and the human F‐box/LRR‐repeat protein 5, which contains a hemerythrin‐like domain, is involved in intracellular iron homeostasis. Furthermore, structural data on hemerythrin‐like domains from two proteins of unknown function, PF0695 from Pyrococcus furiosus and NMB1532 from Neisseria meningitidis, show that the cation‐binding sites, typical of hemerythrin, can be absent or be occupied by metal ions other than iron. To systematically investigate this functional and structural diversity of the hemerythrin‐like superfamily, we have collected hemerythrin‐like sequences from a database comprising fully sequenced proteomes and generated a cluster map based on their all‐against‐all pairwise sequence similarity. Our results show that the hemerythrin‐like superfamily comprises a large number of protein families which can be classified into three broad groups on the basis of their cation‐coordinating residues: (a) signal‐transduction and oxygen‐carrier hemerythrins (H‐HxxxE‐HxxxH‐HxxxxD); (b) hemerythrin‐like (H‐HxxxE‐H‐HxxxE); and, (c) metazoan F‐box proteins (H‐HExxE‐H‐HxxxE). Interestingly, all but two hemerythrin‐like families exhibit internal sequence and structural symmetry, suggesting that a duplication event may have led to the origin of the hemerythrin domain. 相似文献
14.
节肢动物血蓝蛋白家族的组成与演化 总被引:1,自引:0,他引:1
血蓝蛋白是动物界的三类呼吸功能蛋白之一,目前仅发现于节肢动物和软体动物等少数动物类群中。不同亚型的血蓝蛋白有不同的理化性质和序列,但均结合氧分子,并以六聚体,甚至更复杂的聚合体结构存在。血蓝蛋白与酚氧化酶、拟血蓝蛋白、昆虫储存蛋白以及昆虫储存蛋白受体等结构类似、进化上近缘的分子共同组成了血蓝蛋白超家族。该文主要介绍了血蓝蛋白家族成员在节肢动物四大类群(螯肢动物、多足动物、甲壳动物和六足动物)中已知的分布、结构和功能,并重点综述了血蓝蛋白家族成员在节肢动物系统演化研究中发挥的独特而有效的作用,进一步强调了在更多节肢动物类群中研究血蓝蛋白家族的功能和演化的重要性。 相似文献
15.
L. H. Weaver M. G. Grütter S. J. Remington T. M. Gray N. W. Isaacs B. W. Matthews 《Journal of molecular evolution》1985,21(2):97-111
Summary The three-dimensional structure of goose-type lysozyme (GEWL), determined by x-ray crystallography and refined at high resolution, has similarities to the structures of hen (chicken) eggwhite lysozyme (HEWL) and bacteriophage T4 lysozyme (T4L). The nature of the structural correspondence suggests that all three classes of lysozyme diverged from a common evolutionary precursor, even though their amino acid sequences appear to be unrelated (Grütter et al. 1983).In this paper we make detailed comparisons of goose-type, chicken-type, and phage-type lysozymes. The lysozymes have undergone conformational changes at both the blobal and the local level. As in the globins, there are corresponding -helices that have rigid-body displacements relative to each other, but in some cases corresponding helices have increased or decreased in length, and in other cases there are helices in one structure that have no counterpart in another.Independent of the overall structural correspondence among the three lysozyme backbones is another, distinct correspondence between a set of three consecutive -helices in GEWL and three consecutive -helices in T4L. This structural correspondence could be due, in part, to a common energetically favorable contact between the first and the third helices.There are similarities in the active sites of the three lysozymes, but also one striking difference. Glu 73 (GEWL) spatially corresponds to Glu 35 (HEWL) and to Glu 11 (T4L). On the other hand, there are two aspartates in the GEWL active site, Asp 86 and Asp 97, neither of which corresponds exactly to Asp 52 (HEWL) or Asp 20 (T4L). (The discrepancy in the location of the carboxyl groups is about 10 Å for Asp 86 and 4 Å for Asp 97.) This lack of structural correspondence may reflect some differences in the mechanisms of action of three lysozymes. When the amino acid sequences of the three lysozyme types are aligned according to their structural correspondence, there is still no apparent relationship between the sequences except for possible weak matching in the vicinity of the active sites. 相似文献
16.
Shigeki Kimura Tomohiko Hayano Kanefusa Kato 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,799(3):252-259
Two monoclonal antibodies to human and bovine neuron-specific γγ enolase have been produced in the isolated hybrid cell lines, which were obtained by fusion between γγ-immunized mouse spleen cells and mouse myeloma cells (P3-NS-1/1-Ag4-1), followed by a screening procedure with an enzyme immunoassay. The monoclonal antibody to human γγ enolase (E1-G3) and that to bovine γγ enolase (B1-D6) consisted of γ2a/κ and γl/κ immunoglobulin chains, respectively. Both antibodies could bind with the respective antigen with a molar ratio of about 1:1, and were found to be specific for the γ subunit of enolase, showing reactivities with human γγ and αγ, rat γγ and αγ, and bovine γγ enolases. However, the antibodies did not cross-react with the α or β subunit of human and rat enolase isozymes. Both antibodies could partially inhibit the activity of γγ and αγ enolases. E1-G3 antibody inhibited γγ and αγ enolase activity by 70 and 30%, respectively, and B1-D6 antibody, by 90 and 40%, respectively. Both antibodies had no effect on the activity of αα and ββ enolases of human and rat origins. The applicability of E1-G3 and B1-D6 antibodies to the sandwich-type enzyme immunoassay for neuron-specific enolase (enolase γ subunit) was examined, and it was found that the assay system using E1-G3 and B1-D6 as the labeled antibodies were sufficiently sensitive for the assay of serum neuron-specific enolase concentrations. 相似文献
17.
Nucleoside phosphorylases are essential for the salvage and catabolism of nucleotides in bacteria and other organisms, and members of this enzyme superfamily have been of interest for the development of antimicrobial and cancer therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of different enzymes which share a general superfold and catalytic mechanism, while they differ in the nature of the nucleophiles used and in the nature of characteristic active site residues. Recently, one subfamily, the uridine phosphorylases, has been subdivided into two types which differ with respect to the mechanism of transition state stabilization, as dictated by differences in critical amino acid residues. Little is known about the phylogenetic distribution and relationship of the two different types, as well as the relationship to other NP-1 superfamily members. Here comparative genomic analysis illustrates that UP-1s and UP-2s fall into monophyletic groups and are biased with respect to species representation. UP-1 evolved in Gram negative bacteria, while Gram positive species tend to predominantly contain UP-2. PNP (a sister clade to all UPs) contains both Gram positive and Gram negative species. The findings imply that the nucleoside phosphorylase superfamily 1 evolved through a series of three important duplications, leading to the separate, monophyletic enzyme families, coupled to individual lateral transfer events. Extensive horizontal transfer explains the occurrence of unexpected uridine phosphorylases in some genomes. This study provides a basis for understanding the evolution of uridine and purine nucleoside phosphorylases with respect to DNA/RNA metabolism and with potential utility in the design of antimicrobial and anti-tumor drugs. 相似文献
18.
Labbé M Péroval M Bourdieu C Girard-Misguich F Péry P 《International journal for parasitology》2006,36(14):1443-1452
Two cDNA codings for glycolytic enzymes were cloned from a cDNA library constructed from the schizont stage of the avian parasite Eimeria tenella. Enolase and pyruvate kinase cDNA were fully sequenced and compared with sequences of enzymes from other organisms. Although these enzymes were already detected in the sporozoite stage, their expression was enhanced during the first schizogony in accordance with the anaerobic conditions of this part of the life cycle of the parasite. Under activating conditions, microscopic observations suggest that these glycolytic enzymes were relocalised inside sporozoites and moreover were in part secreted. The enzymes were also localised at the apex of the first generation of merozoites. Enolase was partly observed inside the nucleus of sporozoites and schizonts. Taken together, these results suggest that glycolytic enzymes not only have a function in glycolysis during anaerobic intracellular stages but may also participate in the invasion process and, for enolase, in the control of gene regulation. 相似文献
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20.
Molecular characterization of the Entamoeba histolytica enolase gene and modelling of the predicted protein 总被引:1,自引:0,他引:1
María Eugenia Hidalgo Roberto Sánchez D.Guillermo Pérez Mario A Rodríguez Job García Esther Orozco 《FEMS microbiology letters》1997,148(2):123-129
Entamoeba histolytica obtains its energy mainly from glucose fermentation. Enzymes involved in this pathway could be potential targets for antiparasite drugs. Here we report the molecular characterization of the E. histolytica enolase gene (Ehenl-1), which in a single copy is located on the 1.6 Mb chromosome. It is transcribed into a 1.4 kb mRNA which starts 13 nucleotides upstream of the ATG start codon. The sequence TATAAG, at −31, interacted with nuclear proteins suggesting that it has a TATA box function. Protein modelling allowed us to identify a putative specific region that differs from human enolase and could be a good target for the design of novel drugs against E. histolytica. 相似文献