Structural Biology (Dr Teh Aik Hong, Nor Azura Azami)

About

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.
Structure of HGbRL

Research

PHA

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.
 
Alginate Lyase

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 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.
 
DHA

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

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.
 
HGbRL

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.
 

Publications

  1. Crystal structure of Anoxybacillus α-amylase provides insights into maltose binding of a new glycosyl hydrolase subclass
    Chai KP, Othman NF, Teh AH, Ho KL, Chan KG, Shamsir MS, Goh KM, Ng CL
    Scientific Reports 6, 23126 (2016)

  2. Cloning, expression, purification, crystallization and X-ray crystallographic analysis of recombinant human C1ORF123 protein
    Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Ho KL, Teh AH, Waterman J, Ng CL
    Acta Crystallogr F Struct Biol Commun 72, 207–213 (2016)

  3. Cloning, expression, purification, characterization, crystallization and X-ray crystallographic analysis of recombinant Der f 21 (rDer f 21) from Dermatophagoides farinae
    Pang SL, Ho KL, Waterman J, Teh AH, Chew FT, Ng CL
    Acta Crystallogr F Struct Biol Commun 71, 1396–1400 (2015)

  4. Open and Lys–His hexacoordinated closed structures of a globin with swapped proximal and distal sites
    Aik-Hong Teh, Jennifer A. Saito, Nazalan Najimudin, Maqsudul Alam
    Scientific Reports 5, 11407 (2015)

  5. Structure of the RsbX phosphatase involved in the general stress response of Bacillus subtilis
    Aik-Hong Teh, Masatomo Makino, Takeshi Hoshino, Seiki Baba, Nobutaka Shimizu, Masaki Yamamoto, Takashi Kumasaka
    Acta Crystallographica Section D: Biological Crystallography 71, 1392–1399 (2015)

  6. Crystal structure of truncated hemoglobin from an extremely thermophilic and acidophilic bacterium
    Farrukh Jamil, Aik-Hong Teh, Ermin Schadich, Jennifer A. Saito, Nazalan Najimudin, Maqsudul Alam
    Journal of Biochemistry 156, 97–106 (2014)

  7. Crystal structure of a compact α-amylase from Geobacillus thermoleovorans
    Sook-Chen Mok, Aik-Hong Teh, Jennifer A. Saito, Nazalan Najimudin, Maqsudul Alam
    Enzyme and Microbial Technology 53, 46–54 (2013)

  8. Hell’s Gate globin I: An acid and thermostable bacterial hemoglobin resembling mammalian neuroglobin
    Aik-Hong Teh, Jennifer A. Saito, Aida Baharuddin, Jason R. Tuckerman, James S. Newhouse, Masaomi Kanbe, Elizabeth I. Newhouse, Rashidah Abdul Rahim, Frédérique Favier, Claude Didierjean, Eduardo H. S. Sousa, Matthew B. Stott, Peter F. Dunfield, Gonzalo Gonzalez, Marie-Alda Gilles-Gonzalez, Nazalan Najimudin, Maqsudul Alam
    FEBS Letters 585, 3250–3258 (2011)

Protein Crystallography at a Glance

Protein Crystallography