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101.
102.
Chiral intermediates in thiamin catalysis: Resolution and pyrophosphorylation of hydroxyethylthiamin
Ronald Kluger Victoria Stergiopoulos Gerald Gish Khashayar Karimian 《Bioorganic chemistry》1985,13(3):227-234
The improved preparation, resolution, and pyrophosphorylation of hydroxyethylthiamin [HET; 2-(1-hydroxyethyl)thiamin] is reported. HET is the chiral precursor to acetaldehyde, formed in the thiamin-catalyzed decarboxylation of pyruvate. The pyrophosphate, HETDP, is the precursor in the corresponding enzymatic process. Resolution of racemic HET was accomplished by formation of the dibenzoyltartrate salt, repeated crystallization from ethanol, and liberation of resolved HET from the resolving agent with 3 m hydrochloric acid. The optical rotation of the isolated material is comparable to that of the diphosphate derivative that has been isolated from an enzymatic reaction. Conversion of HET to the diphosphate provided material that was active in enzymic reactions. 相似文献
103.
Two novel gene orders and the role of light-strand replication in rearrangement of the vertebrate mitochondrial genome 总被引:14,自引:8,他引:14
Macey JR; Larson A; Ananjeva NB; Fang Z; Papenfuss TJ 《Molecular biology and evolution》1997,14(1):91-104
Two novel mitochondrial gene arrangements are identified in an agamid
lizard and a ranid frog. Statistical tests incorporating phylogeny indicate
a link between novel vertebrate mitochondrial gene orders and movement of
the origin of light-strand replication. A mechanism involving errors in
light-strand replication and tandem duplication of genes is proposed for
rearrangement of vertebrate mitochondrial genes. A second mechanism
involving small direct repeats also is identified. These mechanisms
implicate gene order as a reliable phylogenetic character. Shifts in gene
order define major lineages without evidence of parallelism or reversal.
The loss of the origin of light-strand replication from its typical
vertebrate position evolves in parallel and, therefore, is a less reliable
phylogenetic character. Gene junctions also evolve in parallel. Sequencing
across multigenic regions, in particular transfer RNA genes, should be a
major focus of future systematic studies to locate novel gene orders and to
provide a better understanding of the evolution of the vertebrate
mitochondrial genome.
相似文献
104.
Jennifer Yinuo Cao Kathy Shire Cameron Landry Gerald D. Gish Tony Pawson Lori Frappier 《Molecular and cellular biology》2014,34(2):246-258
Casein kinase 2 (CK2) regulates multiple cellular processes and can promote oncogenesis. Interactions with the CK2β regulatory subunit of the enzyme target its catalytic subunit (CK2α or CK2α′) to specific substrates; however, little is known about the mechanisms by which these interactions occur. We previously showed that by binding CK2β, the Epstein-Barr virus (EBV) EBNA1 protein recruits CK2 to promyelocytic leukemia (PML) nuclear bodies, where increased CK2-mediated phosphorylation of PML proteins triggers their degradation. Here we have identified a KSSR motif near the dimerization interface of CK2β as forming part of a protein interaction pocket that mediates interaction with EBNA1. We show that the EBNA1-CK2β interaction is primed by phosphorylation of EBNA1 on S393 (within a polyserine region). This phosphoserine is critical for EBNA1-induced PML degradation but does not affect EBNA1 functions in EBV replication or segregation. Using comparative proteomics of wild-type (WT) and KSSR mutant CK2β, we identified an uncharacterized cellular protein, C18orf25/ARKL1, that also binds CK2β through the KSSR motif and show that this involves a polyserine sequence resembling the CK2β binding sequence in EBNA1. Therefore, we have identified a new mechanism of CK2 interaction used by viral and cellular proteins. 相似文献
105.
Braunstein M Griffin TJ IV Kriakov JI Friedman ST Grindley ND Jacobs WR 《Journal of bacteriology》2000,182(10):2732-2740
Secreted and cell envelope-associated proteins are important to both Mycobacterium tuberculosis pathogenesis and the generation of protective immunity to M. tuberculosis. We used an in vitro Tn552'phoA transposition system to identify exported proteins of M. tuberculosis. The system is simple and efficient, and the transposon inserts randomly into target DNA. M. tuberculosis genomic libraries were targeted with Tn552'phoA transposons, and these libraries were screened in M. smegmatis for active PhoA translational fusions. Thirty-two different M. tuberculosis open reading frames were identified; eight contain standard signal peptides, six contain lipoprotein signal peptides, and seventeen contain one or more transmembrane domains. Four of these proteins had not yet been assigned as exported proteins in the M. tuberculosis databases. This collection of exported proteins includes factors that are known to participate in the immune response of M. tuberculosis and proteins with homologies, suggesting a role in pathogenesis. Nine of the proteins appear to be unique to mycobacteria and represent promising candidates for factors that participate in protective immunity and virulence. This technology of creating comprehensive fusion libraries should be applicable to other organisms. 相似文献
106.
Li SC Gish G Yang D Coffey AJ Forman-Kay JD Ernberg I Kay LE Pawson T 《Current biology : CB》1999,9(23):1355-1362
BACKGROUND: The Src homology 2 (SH2) domains of cytoplasmic signaling proteins generally bind phosphotyrosine (pTyr) sites in the context of carboxy-terminal residues. SAP (also known as SH2D1A or DSHP), the product of the gene that is mutated in human X-linked lymphoproliferative (XLP) disease, comprises almost exclusively a single SH2 domain, which may modulate T-cell signaling by engaging T-cell co-activators such as SLAM, thereby blocking binding of other signaling proteins that contain SH2 domains. The SAP-SLAM interaction can occur in a phosphorylation-independent manner. RESULTS: To characterize the interaction between SAP and SLAM, we synthesized peptides corresponding to the SAP-binding site at residue Y281 in SLAM. Both phosphorylated and non-phosphorylated versions of an 11-residue SLAM peptide bound SAP, with dissociation constants of 150 nM and 330 nM, respectively. SLAM phosphopeptides that were truncated either at the amino or carboxyl terminus bound with high affinity to SAP, suggesting that the SAP SH2 domain recognizes both amino-terminal and carboxy-terminal sequences relative to the pTyr residue. These results were confirmed by nuclear magnetic resonance (NMR) studies on (15)N- and (13)C-labeled SAP complexed with three SLAM peptides: an amino-terminally truncated phosphopeptide, a carboxy-terminally truncated phosphopeptide and a non-phosphorylated Tyr-containing full-length peptide. CONCLUSIONS: The SAP SH2 domain has a unique specificity. Not only does it bind peptides in a phosphorylation-independent manner, it also recognizes a pTyr residue either preceded by amino-terminal residues or followed by carboxy-terminal residues. We propose that the three 'prongs' of a peptide ligand (the amino and carboxyl termini and the pTyr) can engage the SAP SH2 domain, accounting for its unusual properties. These data point to the flexibility of modular protein-interaction domains. 相似文献
107.
108.
Guettler S LaRose J Petsalaki E Gish G Scotter A Pawson T Rottapel R Sicheri F 《Cell》2011,147(6):1340-1354
The poly(ADP-ribose)polymerases Tankyrase 1/2 (TNKS/TNKS2) catalyze the covalent linkage of ADP-ribose polymer chains onto target proteins, regulating their ubiquitylation, stability, and function. Dysregulation of substrate recognition by Tankyrases underlies the human disease cherubism. Tankyrases recruit specific motifs (often called RxxPDG "hexapeptides") in their substrates via an N-terminal region of ankyrin repeats. These ankyrin repeats form five domains termed ankyrin repeat clusters (ARCs), each predicted to bind substrate. Here we report crystal structures of a representative ARC of TNKS2 bound to targeting peptides from six substrates. Using a solution-based peptide library screen, we derive a rule-based consensus for Tankyrase substrates common to four functionally conserved ARCs. This 8-residue consensus allows us to rationalize all known Tankyrase substrates and explains the basis for cherubism-causing mutations in the Tankyrase substrate 3BP2. Structural and sequence information allows us to also predict and validate other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and MERIT40. 相似文献
109.
Evolutionary relationships among the male and female mitochondrial DNA lineages in the Mytilus edulis species complex 总被引:1,自引:0,他引:1
A novel form of mitochondrial DNA (mtDNA) inheritance has previously been
documented for the blue mussel (Mytilus edulis). Female mussels inherit
their mtDNA solely from their mother while males inherit mtDNA from both
their mother and their father. In males, the paternal mtDNA is
preferentially amplified so that the male gonad is highly enriched for the
paternal mtDNA that is then transmitted from fathers to sons. We
demonstrate that this mode of mtDNA inheritance also operates in the
closely related species M. galloprovincialis and M. trossulus. The
evolutionary relationship between the male and female mtDNA lineages is
estimated by phylogenetic analysis of 455 nucleotides from the large
subunit ribosomal RNA gene. We have found that the male and female lineages
are highly divergent; the divergence of these lineages began prior to the
speciation of the three species of blue mussels. Further, the separation
between the male and female lineages is estimated to have occurred between
5.3 and 5.7 MYA.
相似文献
110.
Kitching R Wong MJ Koehler D Burger AM Landberg G Gish G Seth A 《Biochimica et biophysica acta》2003,1639(2):104-112
A breast cancer-associated mRNA originally cloned as a 475-bp partial cDNA from a library enriched for tumour cDNAs [Oncogene 16 (1998) 327] is expressed at high levels in breast and prostate cancer cells. Immunohistochemical analysis indicates that the protein is expressed in primary breast tumours. We used RT-PCR to generate a full-length 2852 nt mRNA sequence that includes the hypothetical open reading frame (ORF) for human RNF11. Our analysis shows that RNF11 encodes modular domains and motifs likely to interact with other proteins involved in oncogenesis. Chief among these are the RING-H2 finger domain that could facilitate the degradation of specific substrate(s) involved in oncogenesis and the PY motif which binds to WW-domain proteins, several of which are known to be E3 ubiquitin ligases. Our GST-pulldown and immunoprecipitation results indicate that RNF11 interacts with the E3 ligase AIP4 when coexpressed with RNF11 in mammalian cells. 相似文献