Biomedical subjects

Jianming Liu

Publications and source records attributed to Jianming Liu.

7 recordsLinked to original sources

PubMed2006

Two conformations of a crystalline human tRNA synthetase-tRNA complex: implications for protein synthesis.

Aminoacylation of tRNA is the first step of protein synthesis. Here, we report the co-crystal structure of human tryptophanyl-tRNA synthetase and tRNATrp. This enzyme is reported to interact directly with elongation factor 1alpha, which carries charged tRNA to the ribosome. Crystals were generated from a 50/50% mixture of charged and uncharged tRNATrp. These crystals captured two conformations of the complex, which are nearly identical with respect to the protein and a bound tryptophan. They are distinguished by the way tRNA is bound. In one, uncharged tRNA is bound across the dimer, with anticodon and acceptor stem interacting with separate subunits. In this cross-dimer tRNA complex, the class I enzyme has a class II-like tRNA binding mode. This structure accounts for biochemical investigations of human TrpRS, including species-specific charging. In the other conformation, presumptive aminoacylated tRNA is bound only by the anticodon, the acceptor stem being free and having space to interact precisely with EF-1alpha, suggesting that the product of aminoacylation can be directly handed off to EF-1alpha for the next step of protein synthesis.

Amino Acid Sequence↗

PubMed2006

[Promotion of wound healing through incorporation of bFGF-impregnated microspheres into collagen membrane].

OBJECTIVE: To investigate the promotion effects of the collagen membrane incorporating bFGF-impregnated microspheres on the wound healing of the pig skin losing its full-thickness layers. METHODS: The bFGF containing microspheres was added into the dry microspheres. The collagen membranes were prepared by incorporating bFGF-impregnated microspheres, and 6 York pig models of skin wounds with loss of their full-thickness layers were established for the observation of the effects on the wound healing. RESULTS: The healing time and the 28-day healing rate were 27.30 +/- 1.14 days and 98. 12% +/- 1.97%, respectively. The healing rate was significantly higher and the healing time was significantly shorter in the experimental group than in the control group (P < 0.05). The histological examination showed that the proliferation condition of the epidermis was also much better in the experimental group. CONCLUSION: Incorporation of bFGF-impregnated microspheres into the collagen membrane is a promising method of promoting the healing of the wound with a loss of the full-thickness skin.

Animals↗

PubMed2005

Variant of human enzyme sequesters reactive intermediate.

In cellular environments, coupled hydrolytic reactions are used to force efficient product formation in enzyme-catalyzed reactions. In the first step of protein synthesis, aminoacyl-tRNA synthetases react with amino acid and ATP to form an enzyme-bound adenylate that, in the next step, reacts with tRNA to form aminoacyl-tRNA. The reaction liberates pyrophosphate (PP(i)) which, in turn, can be hydrolyzed by pyrophosphatase to drive efficient aminoacylation. A potential polymorphic variant of human tryptophanyl-tRNA synthetase is shown here to sequester tryptophanyl adenylate. The bound adenylate does not react efficiently with the liberated PP(i) that normally competes with tRNA to resynthesize ATP and free amino acid. Structural analysis of this variant showed that residues needed for binding ATP phosphates and thus PP(i) were reoriented from their conformations in the structure of the more common sequence variant. Significantly, the reorientation does not affect reaction with tRNA, so that efficient aminoacylation is achieved.

Adenosine Monophosphate↗

PubMed2004

Suppression of invasion in human U87 glioma cells by adenovirus-mediated co-transfer of TIMP-2 and PTEN gene.

TIMPs and PTEN are known to be inhibitors of the invasive activities of malignant glioma. But there has been no literature reported concerning the effect of combined gene transfer of these two genes on invasiveness of glioma. This study was designed to evaluate the effect of adenovirus-mediated in vitro gene transfer of tissue inhibitor of metalloproteinases-2 (TIMP-2) and phosphatase and tensin homology deleted on chromosome ten (PTEN) on invasion of human U87 glioma cells. The mRNA and protein expressions of TIMP-2 and PTEN in U87 cells infected with AdTIMP-2 and AdPTEN were determined by RT-PCR and Western blot, respectively. The relative activity of MMP-2 and MMP-9 were measured by Gelatin zymogram and invasion of U87 in vitro were detected using Boyden chamber. The number of invasion cell of U87, U87 infected with Ad-gal, AdPTEN, AdTIMP-2 and AdPTEN/TIMP-2 was 55.63+/-13.27, 48.27+/-14.75, 35.27+/-10.94, 27.37+/-12.81, and 19.17+/-5.45, respectively. In vitro invasiveness of glioma cells was significantly inhibited by infection with AdTIMP-2 and/or AdPTEN, which was not consistent with the change of MMPs activity. And in the combinated group, the inhibition effect was more remarkable than in single group. Our studies suggest that adenovirus-mediated combined TIMP-2 and PTEN gene therapy is possibly useful for anti-invasion therapy of malignant glioma.

Adenoviridae↗

PubMed2004

A new gamma-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase.

Two forms of human tryptophanyl-tRNA synthetase (TrpRS) are produced in vivo through alternative mRNA splicing. The two forms, full-length TrpRS and mini TrpRS, are catalytically active, but are distinguished by the striking anti-proliferative and anti-angiogenic activity specific to mini TrpRS. Here we describe two new splice variants of human TrpRS mRNA. Their production was strongly regulated by gamma-interferon (IFN-gamma), an anti-proliferative cytokine known to stimulate the expression of other anti-angiogenic factors. A new IFN-gamma-sensitive promoter was demonstrated to drive production of these splice variants. In human endothelial cells, both the newly discovered and a previously reported promoter were shown to respond specifically to IFN-gamma and not to other cytokines such as tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-4 or erythropoietin. In addition, both promoters were stimulated by the 'downstream' interferon regulatory factor 1 that, in turn, is known to be regulated by the 'upstream' signal transducer and activator of transcription 1alpha subunit. Thus, the tandem promoters provide a dual system to regulate expression and alternative splicing of human TrpRS in vivo.

5' Untranslated Regions↗

PubMed2004

Two new lactones and one new aryl-8-oxa-bicyclo[3,2,1]oct-3-en-2-one from Descurainia sophia.

Two new lactones (1, 2), descurainolide A and B, and one new aryl-8-oxa-bicyclo[3,2,1]-oct-3-en-2-one (3), descurainin, together with five known compounds (4-8), were isolated from the seeds of Descurainia sophia (L.) WEBB ex PRANTL. The structures of the new compounds were elucidated by extensive studies of their 1D, 2D NMR and HR-MS. Compounds 4 and 5 showed cytotoxicity.

Alkenes↗

PubMed2002

Mutational switching of a yeast tRNA synthetase into a mammalian-like synthetase cytokine.

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs. A link was recently established between protein biosynthesis and cytokine signal transduction. Human tyrosyl-tRNA synthetase can be split into two fragments, each of which has a distinct cytokine function. This activity is specific to the human enzyme. It is absent in the enzymes from lower organisms such as bacteria and yeast. Here, yeast tyrosyl-tRNA synthetase (TyrRS), which lacks cytokine activity, was used as a model to explore how a human tyrosyl-tRNA synthetase during evolution acquired novel functions beyond aminoacylation. We found that a rationally designed mutant yeast TyrRS(ELR) gained cytokine function. The mutant yeast enzyme gained this function without sacrifice of aminoacylation activity. Therefore, relatively simple alteration of a basic structural motif imparts cytokine activity to a tRNA synthetase while preserving its canonical function. Further work established that mutational switching of a yeast protein to a mammalian-like cytokine was specific to this synthetase and not to just any yeast ortholog of a mammalian cytokine.

Acylation↗