Biomedical subjects

Wenzhe Ma

Publications and source records attributed to Wenzhe Ma.

6 recordsLinked to original sources

PubMed2006

Robustness and modular design of the Drosophila segment polarity network.

Biomolecular networks have to perform their functions robustly. A robust function may have preferences in the topological structures of the underlying network. We carried out an exhaustive computational analysis on network topologies in relation to a patterning function in Drosophila embryogenesis. We found that whereas the vast majority of topologies can either not perform the required function or only do so very fragilely, a small fraction of topologies emerges as particularly robust for the function. The topology adopted by Drosophila, that of the segment polarity network, is a top ranking one among all topologies with no direct autoregulation. Furthermore, we found that all robust topologies are modular-each being a combination of three kinds of modules. These modules can be traced back to three subfunctions of the patterning function, and their combinations provide a combinatorial variability for the robust topologies. Our results suggest that the requirement of functional robustness drastically reduces the choices of viable topology to a limited set of modular combinations among which nature optimizes its choice under evolutionary and other biological constraints.

Animals↗

PubMed2005

Specificity of trypsin and chymotrypsin: loop-motion-controlled dynamic correlation as a determinant.

Trypsin and chymotrypsin are both serine proteases with high sequence and structural similarities, but with different substrate specificity. Previous experiments have demonstrated the critical role of the two loops outside the binding pocket in controlling the specificity of the two enzymes. To understand the mechanism of such a control of specificity by distant loops, we have used the Gaussian network model to study the dynamic properties of trypsin and chymotrypsin and the roles played by the two loops. A clustering method was introduced to analyze the correlated motions of residues. We have found that trypsin and chymotrypsin have distinct dynamic signatures in the two loop regions, which are in turn highly correlated with motions of certain residues in the binding pockets. Interestingly, replacing the two loops of trypsin with those of chymotrypsin changes the motion style of trypsin to chymotrypsin-like, whereas the same experimental replacement was shown necessary to make trypsin have chymotrypsin's enzyme specificity and activity. These results suggest that the cooperative motions of the two loops and the substrate-binding sites contribute to the activity and substrate specificity of trypsin and chymotrypsin.

Amino Acid Sequence↗

PubMed2005

Construction and expression of a new fusion protein, thymosin alpha1-cBLyS, E. coli.

A fusion thymosin alpha1-soluble B lymphocyte stimulator (TM alpha1-cBLyS) gene was generated to engineer a bifunctional lymphokine, which was then over-produced in Escherichia coli. The molecular weight of the expressed fusion protein was approximately 28 kDa. After being purified by Ni-NTA affinity column, the fusion protein had full activity of BLyS with a slightly higher immunological action than synthetic TMalpha1. Because TM alpha1 regulates the cellular immune response and cBLyS amplifies the humoral response, this bifunctional lymphokine could be useful in the treatment of various immunodeficiency syndromes and serve as an immunomodulator to enhance the host's response to vaccination.

Animals↗

PubMed2004

Two new biologically active illudane sesquiterpenes from the mycelial cultures of Panaeolus retirugis.

Two new illudane sesquiterpenes, paneolic acid and paneolilludinic acid, along with a known antibiotic diterpene, pleuromutilin, were isolated from the mycelial solid cultures of Panaeolus retirugis. Their structures were elucidated on the basis of spectroscopic analysis. Both compounds exhibited antibacterial activity against Staphylococcus aureus, and paneolic acid showed cytotoxicity to HL60 cell with an IC50 of 18.9 microg/ml.

Anti-Bacterial Agents↗

PubMed2003

[Modeling of the SARS coronavirus main proteinase and conformational flexibility of the active site].

SARS coronavirus 3CL proteinase is the key enzyme for virus replication which may serve as the target for drug discovery against SARS. A 3D structure model has been built for SARS coronavirus 3CL proteinase by comparative protein modeling. A homodimer model of the proteinase was also built. Analysis of the dimeric interface suggests the 3CL proteinase may have dimer form in solution. The conformational flexibility of the active site has been simulated by molecular dynamics combined with multi-canonical sampling. The active site loops have two typical conformations which may be related to the conformational movement associated with the enzymatic reaction.

Amino Acid Sequence↗

PubMed2003

New phenolics from Polygala fallax.

Two new phenolic compounds, polygalolide A (1) and polygalolide B (2), together with three known xanthones were isolated from the roots and stems of Polygala fallax. The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence.

Drugs, Chinese Herbal↗