Structural Biology
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In order to understand how proteins function — for example, how they transport oxygen, detect light, fire an electrical impulse, synthesise or break down certain molecules, etc — we need to know their three-dimensional structures. Our group uses X-ray crystallography to solve the structures of proteins.
Research in our group focuses on bacterial and eukaryotic enzymes participating in metabolic pathways such as the synthesis of bioplastics, latex and fatty acids, as well as polysaccharide degradation. We are also working on signalling proteins involved in Salmonella pathogenicity and human mTOR signalling. Presently, we are collaborating with Dr Go Furusawa to study proteins from Mangrovimonas bacteria isolated by his group.
Research in our group focuses on bacterial and eukaryotic enzymes participating in metabolic pathways such as the synthesis of bioplastics, latex and fatty acids, as well as polysaccharide degradation. We are also working on signalling proteins involved in Salmonella pathogenicity and human mTOR signalling. Presently, we are collaborating with Dr Go Furusawa to study proteins from Mangrovimonas bacteria isolated by his group.
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PHA Synthesis
Many bacteria produce polyhydroxyalka-noates (PHAs) as carbon storage. Being biodegradable polymers, PHAs have tremendous industrial and medical uses such as bioplastics and biomaterials, and are synthesized by PHA synthases. Four classes of PHA synthases have been identified, which recognize different monomers to produce PHAs that can have extremely different physical properties. Structural information of these enzymes will not only provide insights into their exact mechanisms, but also form the basis necessary for efficiently engineering them to produce PHAs with the desired properties.
Polysaccharide Degradation
Polysaccharide degrading enzymes have biotechnological applications important to many industries such as food, paper and textile. Alginate lyases degrade an anionic polysaccharide, alginate, which is distributed in the cell walls of brown algae and can constitute up to 40% of their dry weight. Persicobacter sp., a bacterium isolated from a mangrove swamp by Dr Go Furusawa, expresses a unique alginate lyase that contains two additional carbohydrate-binding (CBM and F5/8) domains. As in recent years algal biomass has attracted worldwide attention as raw materials for biofuel production, development of efficient alginate lyases is increasingly important for the degradation of algal cell walls. We also collaborate on a bacterial agarase, whose activity is enhanced by an additional carbohydrate-binding domain.
Toxin–Antitoxin System
Toxin–antitoxin (TA) systems, composed of a toxin and an antitoxin encoded in an operon, are widespread in prokaryotes. The toxin and the antitoxin form a stable nontoxic complex in normal growing cells, but under stress the antitoxin is degraded and the toxin is released to attenuate cell growth. In the course of analyzing several Salmonella genomes, we have come across a new Type II TA system comprising a putative RNase as the toxin. This TA system is conserved not only in S. enterica, but also in pathogenic E. coli strains, Shigella dysenteriae and Klebsiella pneumoniae, indicating a possible role for the system in bacterial pathogenicity.
Fatty Acid Synthesis
Polyunsaturated fatty acids (PUFA), including omega-3 fatty acids such as docosahexaenoic acid (DHA), are pivotal for the normal function and development of vertebrates. Fatty acid desaturases (Fads) are key enzymes in PUFA synthesis that introduce double bonds into fatty acids. In order to understand how Fads enzymes selectively act on specific sites of the long chains of PUFA, we are working on determining the structure of zebrafish Fads2, which comprises an N-terminal cytochrome b5 domain and a C-terminal desaturase domain with two transmembrane regions.
mTOR Signalling
The mTOR (mammalian target of rapamycin) signalling pathway is a central pathway that regulates cell growth and metabolism. The key protein, mTOR, is a huge serine/threonine kinase that forms two distinct complexes to regulate important kinases through phosphory-lation. The regulation of mTOR activity is critical, and deregulation of mTOR signalling has profound effects on lifespan as well as on the development of age-related diseases and cancer in human.
Globins from Extremophile
Globins are heam-containing proteins with functions like transporting, storing and sensing small molecules such as O2. The bacterium Methylacidiphilum infernorum, isolated from Hell's Gate in New Zealand, grows optimally at 60 °C and pH 2.0. Its genome encodes five globins, and we have solved the structures of three of them — HGbI, HGbIV and HGbRL. HGbI has very high affinity for O2 and is exceptionally resistant to oxidation, whereas HGbIV contains a large hydrophilic active site that can bind a phosphate ion. HGbRL, meanwhile, is a putative sensor with an additional domain, forming open and closed structures with swapped proximal and distal sites. These interesting globins most probably have gained some novel functions that help M. infernorum survive in extreme environments.{slider-nested Publications|closed}
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