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1.
Ronda Bransteitter Courtney Prochnow Xiaojiang S. Chen 《Cellular and molecular life sciences : CMLS》2009,66(19):3137-3147
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases has emerged as an intensively
studied field as a result of their important biological functions. These enzymes are involved in lipid metabolism, antibody
diversification, and the inhibition of retrotransposons, retroviruses, and some DNA viruses. The APOBEC proteins function
in these roles by deaminating single-stranded (ss) DNA or RNA. There are two high-resolution crystal structures available
for the APOBEC family, Apo2 and the C-terminal catalytic domain (CD2) of Apo3G or Apo3G-CD2 [Holden et al. (Nature 456:121–124,
2008); Prochnow et al. (Nature 445:447–451, 2007)]. Additionally, the structure of Apo3G-CD2 has also been determined using
NMR [Chen et al. (Nature 452:116–119, 2008); Furukawa et al. (EMBO J 28:440–451, 2009); Harjes et al. (J Mol Biol, 2009)].
A detailed structural analysis of the APOBEC proteins and a comparison to other zinc-coordinating deaminases can facilitate
our understanding of how APOBEC proteins bind nucleic acids, recognize substrates, and form oligomers. Here, we review the
recent development of structural and functional studies that apply to Apo3G as well as the APOBEC deaminase family. 相似文献
2.
Homing endonucleases: structure, function and evolution 总被引:19,自引:0,他引:19
‘Homing’ is the lateral transfer of an intervening genetic sequence, either an intron or an intein, to a cognate allele that
lacks that element. The end result of homing is the duplication of the intervening sequence. The process is initiated by site-specific
endonucleases that are encoded by open reading frames within the mobile elements. Several features of these proteins make
them attractive subjects for structural and functional studies. First, these endonucleases, while unique, may be contrasted
with a variety of enzymes involved in nucleic acid strand breakage and rearrangement, particularly restriction endonucleases.
Second, because they are encoded within the intervening sequence, there are interesting limitations on the position and length
of their open reading frames, and therefore on their structures. Third, these enzymes display a unique strategy of flexible
recognition of very long DNA target sites. This strategy allows these sequences to minimize nonspecific cleavage within the
host genome, while maximizing the ability of the endonuclease to cleave closely related variants of the homing site. Recent
studies explain a great deal about the biochemical and genetic mechanisms of homing, and also about the structure and function
of several representative members of the homing endonuclease families.
Received 6 January 1999; received after revision 24 February 1999; accepted 24 February 1999 相似文献
3.
Maria J. Marcaida Inés G. Muñoz Francisco J. Blanco Jesús Prieto Guillermo Montoya 《Cellular and molecular life sciences : CMLS》2010,67(5):727-748
Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12–40 bp). HE-encoding sequences
are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of
these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate
some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates
to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used
to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes with very low
toxicity levels. The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that
can be treated ex vivo. This review provides an overview of recent advances in this field. 相似文献
4.
Hammerhead ribozyme design and application 总被引:4,自引:0,他引:4
The emerging knowledge about RNA-based enzymes has already had great impact on our concept of evolutionary history, making
the ‘RNA world’ more likely. It may well have an equally important impact on the diagnostic and therapeutic practices of human
and veterinary medicine in the next decade. We are not quite there yet. This review addresses the design and application of
hammerhead ribozymes, two aspects of a conserved and most commonly studied and used enzymatically active entity among the
RNA enzymes. The emerging picture is one of great diversity. There is at this stage no general cell model nor a clearly preferable
ribozyme structure. Each and every cell line (and tissue) may be unique in that they vary with respect to structural requirements
for optimal uptake, activity and stability of ribozymes. We may have seen only the tip of the iceberg when it comes to RNA-based
enzymes and their roles in biology and medicine.
Received 3 June 1998; received after revision 28 July 1998; accepted 28 July 1998 相似文献
5.
Brakmann S 《Cellular and molecular life sciences : CMLS》2005,62(22):2634-2646
Polynucleotide polymerases play a crucial role in transmitting genetic information from generation to generation, and they
are the most important reagents in biotechnology. Although classical crystal structure analyses as well as biochemical studies
have significantly contributed to our understanding of how DNA polymerases function, surprising new insights regarding the
importance of certain residues and protein motifs, or of their mutability have been achieved in recent years by evolutionary
approaches. Directed evolution has also facilitated the generation of polymerases with tailored substrate repertoires or with
stabilities and activities beyond those of their naturally evolved counterparts. Recent new insights in polymerase structure-function
relationships and new achievements in the development of tailored polymerases for current methods of nucleic acid synthesis
will be summarized in this article.
Received 22 April 2005; received after revision 20 July 2005; accepted 27 July 2005 相似文献
6.
Hepatitis C virus (HCV) translation is mediated by an internal ribosome entry site (IRES) located at the 5′ end of the genomic
RNA. The 3′ untranslatable region (3′UTR) stimulates translation by the recruitment of protein factors that simultaneously
bind to the 5′ end of the viral genome. This leads to the formation of a macromolecular complex with a closed loop conformation,
similar to that described for the cap-translated mRNAs. We previously demonstrated the existence of a long-range RNA–RNA interaction
involving subdomain IIId of the IRES region and the stem–loop 5BSL3.2 of the CRE element at the 3′ end of the viral genome.
The present study provides evidence that the enhancement of HCV IRES-dependent translation mediated by the 3′UTR is negatively
controlled by the CRE region in the human hepatoma cell lines Huh-7 and Hep-G2 in a time-dependent manner. Domain 5BSL3.2
is the major partner in this process. Mutations in this motif lead to an increase in IRES activity by up to eightfold. These
data support the existence of a functional high order structure in the HCV genome that involves two evolutionarily conserved
RNA elements, domain IIId in the IRES and stem–loop 5BSL3.2 in the CRE region. This interaction could have a role in the circularisation
of the viral genome. 相似文献
7.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献
8.
The public perception of selenium has changed significantly over the last decades. Originally mainly known for its high toxicity,
it was later recognized as an essential trace element and is now (despite its narrow therapeutic window) almost being marketed
as a lifestyle drug. Indeed, some clinical and preclinical studies suggest that selenium supplementation may be beneficial
in a large number of clinical conditions. However, its mode of action is unresolved in most of these cases. Selenocysteine
– identified as the 21st amino acid used in ribosome-mediated protein synthesis – is incorporated in at least 25 specific, genetically determined
human selenoproteins, many of which have only recently been discovered. Restoration of normal selenoprotein levels may be
– apart from direct supranutritional effects – one possible explanation for the effects of selenium supplements. In this review
we provide a brief but up-to-date overview of what is currently known about these 25 acknowledged human selenoproteins and
their synthesis.
Received 30 March 2005; received after revision 4 July 2005; accepted 13 July 2005 相似文献
9.
A. Gerson-Gurwitz N. Movshovich R. Avunie V. Fridman K. Moyal B. Katz M. A. Hoyt L. Gheber 《Cellular and molecular life sciences : CMLS》2009,66(2):301-313
S. cerevisiae anaphase spindle elongation is accomplished by the overlapping function of dynein and the kinesin-5 motor proteins, Cin8
and Kip1. Cin8 and dynein are synthetically lethal, yet the arrest phenotypes of cells eliminated for their function had not
been identified. We found that at a non-permissive temperature, dyn1Δ cells that carry a temperature-sensitive cin8 – 3 mutation arrest at mid-anaphase with a unique phenotype, which we named TAN (two microtubule asters in one nucleus). These
cells enter anaphase, but fail to proceed through the slow phase of anaphase B. At a permissive temperature, dyn1Δ, cin8 – 3 or dyn1Δcin8 – 3 cells exhibit perturbed spindle midzone morphologies, with dyn1Δcin8 – 3 anaphase spindles also being profoundly bent and nonrigid. Sorbitol, which has been suggested to stabilize microtubules,
corrects these defects and suppresses the TAN phenotype. We conclude that dynein and Cin8 cooperate in anaphase midzone organization
and influence microtubule dynamics, thus enabling progression through the slow phase of anaphase B.
Received 10 August 2008; received after revision 22 October 2008; accepted 27 October 2008 相似文献
10.
Poelarends GJ Veetil VP Whitman CP 《Cellular and molecular life sciences : CMLS》2008,65(22):3606-3618
Tautomerase superfamily members have an amino-terminal proline and a β–α–β fold, and include 4-oxalocrotonate tautomerase
(4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), malonate semialdehyde decarboxylase (MSAD), and macrophage migration inhibitory factor (MIF), which
exhibits a phenylpyruvate tautomerase (PPT) activity. Pro-1 is a base (4-OT, CHMI, the PPT activity of MIF) or an acid (CaaD,
cis-CaaD, MSAD). Components of the catalytic machinery have been identified and mechanistic hypotheses formulated. Characterization
of new homologues shows that these mechanisms are incomplete. 4-OT, CaaD, cis-CaaD, and MSAD also have promiscuous activities with a hydratase activity in CaaD, cis-CaaD, and MSAD, PPT activity in CaaD and cis-CaaD, and CaaD and cis-CaaD activities in 4-OT. The shared promiscuous activities provide evidence for divergent evolution from a common ancestor,
give hints about mechanistic relationships, and implicate catalytic promiscuity in the emergence of new enzymes.
Received 22 May 2008; received after revision 20 June 2008; accepted 02 July 2008 相似文献
11.
The inhibitory effect of esters of p-hydroxybenzoic acid (kelletinins I and A), extracted from the marine gastropod Buccinulum corneum, have been tested on eukaryotic and prokaryotic enzymes of DNA metabolism such as DNA polymerases alpha and beta, DNA polymerase I, Exo III, pancreatic DNAse I, micrococcal DNAse and E. coli RNA polymerase. Kelletinin I and kelletinin A inhibit preferentially DNA polymerase alpha. The inhibitory effect of kelletinin I involves the hydroxyl group of p-hydroxybenzoic acid. 相似文献
12.
Heat shock protein 60: regulatory role on innate immune cells 总被引:1,自引:0,他引:1
Human heat shock protein 60 (Hsp60) exhibits immunoregulatory properties, primarily by inducing pro-inflammatory responses
in innate immune cells. Extensive analyses identified specific receptor structures for the interaction of Hsp60 with these
cells. The existence of distinct receptor structures responsible for Hsp60 binding and for Hsp60-induced release of pro-inflammatory
mediators has been demonstrated, implying that the interaction of Hsp60 with innate immune cells is a multifaceted process.
Distinct Hsp60 epitopes responsible for binding to innate immune cells and for the activation of these cells have been identified.
Depending on the cell-type, the amino acid (aa) region 481–500 or the regions aa241–260, aa391–410 and aa461–480 are involved
in Hsp60-binding to innate immune cells. An entirely different Hsp60-region, aa354–365 was found to bind lipopolysaccharide,
thereby mediating the pro-inflammatory effects of Hsp60. Because of its immunoregulatory properties, Hsp60 has been proposed
to act as intercellular danger signal, controlling innate and adaptive immune reactions.
Received 19 September 2006; received after revision 13 October 2006; accepted 13 December 2006 相似文献
13.
The focus of this review is the M-superfamily of Conus venom peptides. Disulfide rich peptides belonging to the M-superfamily have three loop regions and the cysteine arrangement:
CC–C–C–CC, where the dashes represent loops one, two, and three, respectively. Characterization of M-superfamily peptides
has demonstrated that diversity in cystine connectivity occurs between different branches of peptides even though the cysteine
pattern remains consistent. This superfamily is subdivided into five branches, M-1 through M-5, based on the number of residues
in the third loop region, between the fourth and fifth cysteine residues. M-superfamily peptides appear to be ubiquitous in
Conus venom. They are largely unexplained in indigenous biological function, and they represent an active area of research within
the scientific community. 相似文献
14.
Liangmei He Yayun Chen Yuanbing Wu Ying Xu Zixiang Zhang Zhiping Liu 《Cellular and molecular life sciences : CMLS》2017,74(13):2395-2411
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36). Activation of these receptors eventually leads to the release of cytokines and activation of immune cells, which are well known to play crucial roles in host defense against intracellular bacterial and virus infection. However, the functions of these nucleic acid sensing PRRs in the other diseases such as CRC and colitis remain largely unknown. Recent studies indicated that nucleic acid sensing PRRs contribute to CRC and/or colitis development, and therapeutic modulation of nucleic acid sensing PRRs may reduce the risk of CRC development. However, until now, a comprehensive review on the role of nucleic acid sensing PRRs in CRC and colitis is still lacking. This review provided an overview of the roles as well as the mechanisms of these nucleic acid sensing PRRs (AIM2, STING, cGAS, RIG-I and its downstream molecules, DDX3, 5, 6,17, and DHX9, 36) in CRC and colitis, which may aid the diagnosis, therapy, and prognostic prediction of CRC and colitis. 相似文献
15.
Hcc-1 is a novel nuclear protein containing the SAF-box DNA-binding domain. It binds to both double-stranded and single-stranded DNA with higher affinity for the single-stranded form. In addition, it also binds specifically to scaffold/matrix attachment region DNA. These nucleic acid-binding characteristics suggest a potential function for Hcc-1 as a component of the heterogeneous ribonucleoprotein complex. Using a yeast two-hybrid screen, two DEAD-box RNA helicases, BAT1 and DDX39, were identified as proteins that interact with Hcc-1. Interactions with these RNA helicases suggested a role for Hcc-1 in nucleic acid biogenesis. Expression of Hcc-1 in the HEK293 cell line resulted in a slower growth rate compared to controls (p = 0.0173) and an accumulation of cells at the G2/M phase (p = 0.0276 compared to control HEK293 cells). Taken together, these results suggest a role for Hcc-1 in growth regulation and nucleic acids metabolism.Received 13 May 2004; received after revision 30 June 2004; accepted 6 July 2004 相似文献
16.
G. M. Rossolini S. Schippa M. L. Riccio F. Berlutti L. E. Macaskie M. C. Thaller 《Cellular and molecular life sciences : CMLS》1998,54(8):833-850
Bacterial nonspecific acid phosphohydrolases (NSAPs) are secreted enzymes, produced as soluble periplasmic proteins or as
membrane-bound lipoproteins, that are usually able to dephosphorylate a broad array of structurally unrelated substrates and
exhibit optimal catalytic activity at acidic to neutral pH values. Bacterial NSAPs are monomeric or oligomeric proteins containing
polypeptide components with an M
r of 25 – 30 kDa. On the basis of amino acid sequence relatedness, three different molecular families of NSAPs can be distinguished,
indicated as molecular class A, B and C, respectively. Members of each class share some common biophysical and functional
features, but may also exhibit functional differences. NSAPs have been detected in several microbial taxa, and enzymes of
different classes can be produced by the same bacterial species. Structural and phyletic relationships exist among the various
bacterial NSAPs and some other bacterial and eucaryotic phosphohydrolases. Current knowledge on bacterial NSAPs is reviewed,
together with analytical tools that may be useful for their characterization. An overview is also presented concerning the
use of bacterial NSAPs in biotechnology.
Received 21 November 1997; received after revision 10 March 1998; accepted 10 March 1998 相似文献
17.
E. Seneta 《Archive for History of Exact Sciences》1998,53(3-4):201-213
Historiography of the development of probability and statistics in the Russian Empire focusses on the contributions of the
central figure Pafnutiy Lvovich Chebyshev (1821–1894) and his successors. The purpose of this article is to concentrate on
an earlier period which culminates with Chebyshev, and specifically on two less-than-well-explored aspects:
(1) The background and motivation for his activity in probability and statistics;
(2) The French connections and influences on his work.
The key figures in this account are A.F. Pavlovsky (1789–1875); M.V. Ostrogradsky (1801–1862); V.Y. Buniakovsky (1804–1889);
N.D. Brashman (1796–1866); N.E. Zernov (1804–1862), S.G. Stroganov (1794–1882); P.S. de Laplace (1749–1827); A.L. Cauchy
(1789–1857); I.J. Bienaymé (1796–1878); N.V. Khanykov (1819–1878); and, in Chebyshevs childhood, a governess and relation,
Avdotiia Kvintillianovna Sukhareva. Chief among these, from the years of Chebyshevs maturity, are Buniakovsky and Bienaymé.
The cultural contacts between France and the Russian Empire in the 19th century were strong, and these connections are particularly
well-illustrated in this setting.
(Received January 10, 1998) 相似文献
18.
19.
We summarize the clinical presentation and molecular basis of a unique group of congenital immunodeficiency disorders in which
defects in immune tolerance mechanisms result in severe autoimmunity. Patients with severe, familial forms of multi-organ
autoimmunity have been recognized and clinically described for more than 40 years (Clin Exp Immunol 1: 119–128, 1966; Clin Exp Immunol 2: 19–30, 1967). Some are characterized primarily by autoimmunity and others by autoimmunity combined with susceptibility to specific infectious
organisms. The first mechanistic understanding of these disorders began to emerge approximately 10 years ago with the initial
identification of causative genes. As a result, our understanding of how immune tolerance is established and maintained in
humans has expanded dramatically. Data generated over the last 3–4 years including identification of additional gene defects
and functional characterization of each identified gene product in human and animal models have added clarity. This, in turn,
has improved our ability to diagnose and effectively treat these severe, life-threatening disorders. Inherited disorders characterized
by immune dysregulation have dramatically expanded our understanding of immune tolerance mechanisms in humans. Recognition
and diagnosis of these disorders in the clinic allows timely initiation of life-saving therapies that may prevent death or
irreversible damage to vital organs. 相似文献
20.
Platelet-activating factor acetylhydrolases (PAF-AHs, EC 3.1.1.47) constitute a unique and biologically important family
of phospholipase A2s. They are related to neither the well-characterized secretory nor cytosolic PLA2s, and unlike them do not require Ca2+ for catalytic activity. The distinguishing property of PAF-AHs is their unique substrate specificity they act on the phospholipid
platelet-activating factor (PAF), and in some cases on proinflammatory polar phospholipids, from which they remove a short
acyl moiety – acetyl in the case of PAF – located at the sn-2 position. Because PAF is found both in the plasma and in the cytosol of many tissues, PAF-acetylhydrolases are equally widely
distributed in an animal organism. Recent crystallographic studies shed new light on the complex structure-function relationships
in PAF-AHs.
Received 15 September 1997; received after revision 23 February 1998; accepted 25 February 1998 相似文献