Wanzhi Huang Ph.D.
Protein Structure-Function and Protein-Protein Interaction Studies
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Assistant Professor- Ph.D.
University of Science and Technology of China
- 713-798-5106
wanh@bcm.tmc.edu
TEM-1 ß-lactamase
(29 kDa) is the most prevalent plasmid mediated ß-lactamase
in Gram-negative bacteria. The TEM-1 enzyme provides bacteria
with resistance to ß-lactam antibiotics by catalyzing
the hydrolysis of penicillin and cephalosporins.
The ß-lactamase inhibitory protein (BLIP) is an 18 kDa
protein that binds and inhibits TEM-1 ß-lactamase. We
have constructed a phagemid vector that displays BLIP on the
surface of filamentous phage to study the interaction between
BLIP and TEM-1. We have also constructed a BLIP active-site
amino acid library, cyclic 13-mer peptide library, and a random
BLIP peptide library to further characterize the interaction
between BLIP and TEM-1. The interaction between BLIP and other
proteins that interact with ß-lactam antibiotics, such
as penicillin binding proteins (PBPs), is also being carried
out.
We have identified peptides that bind and inhibit TEM-1 and
PBP’s using a C7C random peptide phage display library
and an auto-spot peptide synthesizer. These results are important
in understanding protein structure-function and protein-protein
interaction. This information is also useful in the design
of ß-lactamase and PBP inhibitors.
Sideraki, V., Huang, W., Palzkill, T., and Gilbert, H.F. (2001). A secondary drug resistance mutation of TEM-1 ß-lactamase that suppresses misfolding and aggregation. Proc. Natl. Acad. Sci. USA 98: 283-288
Rudgers, G., Huang, W., and Palzkill, T. (2001). A ß-turn from ß-lactamase inhibitory protein is sufficient for inhibition of TEM-1 ß-lactamase. Antimicrob. Agents Chemother. 45:3279-3286
Huang, W., and Palzkill, T. (2000). Design of potent ß-lactamase inhibitors by phase display of ß-lactamase inhibitory protein. J. Biol. Chem. 275:14964-14968
Huang, W., McKevitt, M., and Palzkill, T. (2000). Tightly regulated display of protein on bacteriophage using the arabinose PBAD promoter. Gene 251:187-197
Palzkill, T., Huang, W., and Weinstock, G.M. (1998). Mapping protein-protein interactions using whole genome phage display libraries. Gene 221:79-83
Huang, W., Petrosino, J. and Palzkill, T. (1998). Display of functional ß-lactamase inhibitory protein of the surface of M13 bacteriophage. Antimicrob. Agents Chemother. 42: 2893-2898
Huang, W., and
Palzkill, T. (1997). A natural plymorphism in ß-lactamase
is a global suppressor. Proc. Natl. Acad. Sci. USA 94: 8801-8806