The research team, led by Che Alex Ma, an assistant research fellow at Academia Sinica's Genomics Research Center, has successfully developed a complete three-dimensional model structure of the membrane protein that resides on the surface of the bacteria Escherichia coli, the research institute said in a press statement.

This marks the first time that a mechanism that holds the key to bacterial cell wall formation has been disclosed in detail and could lead to the development of a new generation of antibiotocs, the statement said.

Bacteria construct cell walls as they divide and multiply, and antibiotics are effective because they block certain key enzymes that help bacteria build those walls. By deciphering the membrane protein -- in this case penicillin-binding protein 1b (PBP1b) -- Ma's team can better figure out how to block it.

The study immediately attracted attention from the global academic community after it was published May 19 in the online version of the U.S. National Academy of Sciences journal -- the Proceedings of the National Academy of Sciences (PNAS).

Over the past 80 years since the discovery of penicillin, at least 1,000 kinds of antibiotics have been developed to fight off bacterial infections, about 150 of which have been commonly used to treat infections.

However, the rise of drug-resistant bacterial has caused serious medical problems in recent years, making the need for new antibacterial agents more urgent.

Ma started his research five years ago, as part of a project to solve the mystery of bacterial cell wall synthesis and to address the drug-resistance bacterial infection issue, led by Academia Sinica President Chi-Huey Wong.

Initially, Ma and his colleagues studied the activity of penicilin-binding protein (PBPs) and published their work in early 2008 in the PNAS.

The team then focused on discovering exactly how PBP1b conducts the task of making bacterial cell walls. After five years of hard work, the team managed to obtain its three-dimensional structure by coaxing the purified membrane protein PMP1b into crystals and using X-ray crystallography. The resulting model gives a clear picture of how PBP1b binds a substance called lipid II and performs a kind of a knitting job to finally make a new skin when the bacteria divides, according to the research institute's statement.

The team's work also revealed the interaction between PBP1b and moenomycin, the statement said. Moenomycin is an antibiotic that restricts the growth of bacteria by inactivating transglycosylases (TG), enzymes that also help bacteria construct their cell walls.

The team identified one particular area within the structure named "the UB2H domain" that they propose to be a key player in coordinating cell wall formation and DNA synthesis/repair, the statement said.

"We did not envision so many achievements in one shot," exclaimed Ma, "especially, as each one turns on a light that we just cannot resist in pursuing facts that may eventually help fight off bacterial infections." According to Ma, this is the first membrane protein structure that has ever been determined in Taiwan.

Membrane proteins, which make up over 30 percent of all proteins, play critical roles in different biological processes and represent more than 50 percent of current drug targets.

(By Sofia Wu)