Search PubMed⌕ Search

Biomedical subjects

Miao Lu

Publications and source records attributed to Miao Lu.

6 recordsLinked to original sources
PubMed2006

pH dependence of light-driven proton pumping by an archaerhodopsin from Tibet: comparison with bacteriorhodopsin.

The pH-dependence of photocycle of archaerhodopsin 4 (AR4) was examined, and the underlying proton pumping mechanism investigated. AR4 is a retinal-containing membrane protein isolated from a strain of halobacteria from a Tibetan salt lake. It acts as a light-driven proton pump like bacteriorhodopsin (BR). However, AR4 exhibits an "abnormal" feature--the time sequence of proton release and uptake is reversed at neutral pH. We show here that the temporal sequence of AR4 reversed to "normal"--proton release preceding proton uptake--when the pH is increased above 8.6. We estimated the pK(a) of the proton release complex (PRC) in the M-intermediate to be approximately 8.4, much higher than 5.7 of wide-type BR. The pH-dependence of the rate constant of M-formation shows that the pK(a) of PRC in the initial state of AR4 is approximately 10.4, whereas it is 9.7 in BR. Thus in AR4, the chromophore photoisomerization and subsequent proton transport from the Schiff base to Asp-85 is coupled to a decrease in the pK(a) of PRC from 10.4 to 8.4, which is 2 pK units less than in BR (4 units). This weakened coupling accounts for the lack of early proton release at neutral pH and the reversed time sequence of proton release and uptake in AR4. Nevertheless the PRC in AR4 effectively facilitates deprotonation of primary proton acceptor and recovery of initial state at neutral pH. We found also that all pK(a)s of the key amino acid residues in AR4 were elevated compared to those of BR.

Amino Acid Sequence↗
PubMed2006

Native chemical ligation in covalent caspase inhibition by p35.

Wide-spectrum caspase inhibition by the baculoviral p35 protein was previously shown to be a consequence of covalent inhibition in which a thioester bond is stably formed between the cleavage residue Asp87 of p35 and the active site Cys360' of caspase-8. Here we show that the N-terminal fragment of cleaved p35 (p35-N) is a circular peptide when dissociated from the caspase. Biochemical and crystallographic data suggest that p35-N circularization results from the trapping of a native chemical ligation intermediate in the p35/caspase complex, in which the N-terminal Cys2 of p35 attacks the Asp87-Cys360' thioester to form an equilibrium between Asp87-Cys2 and Asp87-Cys360'. This provides a crucial covalent interaction for keeping the N terminus of p35 bound in the caspase active site, which explains the absolute requirement of Cys2 for caspase inhibition. Participation of native chemical ligation in caspase inhibition by p35 illustrates an unusual mechanism of protease inhibition.

Aspartic Acid↗
PubMed2004

Antagonizing XIAP-mediated caspase-3 inhibition. Achilles' heel of cancers?

In this issue of Cancer Cell, Schimmer et al. report the identification of small molecule antagonists of XIAP that overcome its inhibition of caspase-3. It was remarkable that the compounds directly induced cell death in tumor cells while having little toxicity on normal cells. This suggests that caspases are already activated in tumor cells, which is different from the caspase activation status in normal mammalian cells. In comparison with Smac peptides targeting XIAP-mediated caspase-9 inhibition, which do not directly induce cell death, it appears that liberating downstream caspases rather than upstream caspases may be a preferred strategy for cancer drug discovery.

Animals↗
PubMed2004

[Structural modification and bioactivity of cyclovirobuxine D].

AIM: To search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D. METHODS: According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested. RESULTS: Ten new compounds were syntheized and confirmed by spectra. CONCLUSION: Endurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.

Anaerobic Threshold↗
PubMed2004

[An EEG compression algorithm based on embedded zerotree wavelet (EZW)].

OBJECTIVE: To study algorithm with high speed and high compression ratio for EEG signal. METHOD: A wavelet compression algorithm for ECG based on EZW (embedded zerotree wavelet) coding was presented. RESULT: The result of the experiment showed that the algorithm is simple and fast. It can achieve high compression ratio and fidelity. CONCLUSION: The algorithm with high speed and high compression is very effective.

Algorithms↗