Research 

Structural and functional studies of membrane proteins

          Our research is focused on expression and purification of bacteria membrane proteins for x-ray crystallographic studies. To understand their functions, we also carry out biochemical studies with both detergent solublized membrane proteins and in reconstituted proteoliposomes. We use methods such as mutagenesis, optical/electrical stopped-flow, homology modeling and molecular dynamics simulations to probe the mechanisms. To study substrate and inhibitor interactions, we carry out experiments with isothermal titration calorimetry(ITC), surface plasmon resonance(Biacore).

People

Yafei Huang,  Assistant Professor, Vinnmer fellow

B.Sc. 1998 University of Science and Technology of China, Department of Biological Sciences

(1997-1998 Beijing Institute of Biophysics, under-graduate research assistant in Xun Shen's group)

Ph.D. 2002 University of Kansas, USA.  Advisor: Fusao Takusagawa

2002-2005 New York University School of Medicine, USA. postdoc in DaNeng Wang's group 

2005-2006 Stockholm University, Department of Structural Chemistry, postdoc in Sven Hovmöller's group

2006-2008 Stockholm University, Department of Biochemistry and Biophysics, postdoc in Pia Ädelroth's group

Li Zhang Postdoctoral Fellow

2009 Ph.D in Molecular Microbiology, Durham University, UK

2002 M. Phil in Medical Microbiology, Medical School of Xi’an JiaoTong University, China

1998 MD in Clinical Medicine, Medical School of Xi’an JiaoTong University, China

Wangshu Jiang Graduate Student

Affiliations

Department of Molecular Biology, SLU

Uppsala Biomedical Center

Uppsala Structural Biology Consortium

Collaborators

Financial supports

Swedish Research Council

Vinnova

Carl Tryggers Stiftelse för Vetenskaplig Forskning 

Publications

             Huang Y, Reimann J, Singh L and Adelroth P. Substrate binding and the catalytic reactions in cbb3-type oxidases; the lipid membrane modulates    ligand binding. BBA-Bioenergetics 2010, 1797(6-7):724-731     

            Lachmann P, Huang Y, Reimann J and Adelroth P. Substrate control of internal electron transfer in bacterial nitric oxide reductase. J Biol Chem. 2010, 285(33):25531-7               

            Huang Y, Reimann J, Lepp H and Ädelroth P (2008): Vectorial proton transfer coupled to reduction of O2 and NO by a heme-copper oxidase. Proc Natl Acad Sci U S A 105(51): p. 20257-62.

             Law C, Almqvist J, Bernstein A, Goetz R, Huang Y, Soudant C, Laaksonen A, Hovmöller S and Wang DN (2008): Salt bridge dynamics function in conformational change upon substrate binding and transport by GlpT. J. Mol. Biol 378(4):826-37

             Almqvist J, Huang Y, Laaksonen A, Wang DN and Hovmoller S, (2007): Docking and homology modeling explain inhibition of the human vesicular glutamate transporters. Protein Sci 16: 1819-29.

             Lemieux MJ, Huang Y and Wang da N, (2005): Crystal structure and mechanism of GlpT, the glycerol-3-phosphate transporter from E. coli. J Electron Microsc (Tokyo) 54 Suppl 1: i43-i46.

             Lemieux MJ, Huang Y and Wang DN, (2004): Glycerol-3-phosphate transporter of Escherichia coli: structure, function and regulation. Res Microbiol 155: 623-9.

             Lemieux MJ, Huang Y and Wang DN, (2004): The structural basis of substrate translocation by the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily. Curr Opin Struct Biol 14: 405-12.

             Almqvist J, Huang Y, Hovmoller S and Wang DN, (2004): Homology modeling of the human microsomal glucose 6-phosphate transporter explains the mutations that cause the glycogen storage disease type Ib. Biochemistry 43: 9289-97.

            Takata Y, Huang Y, Komoto J, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M and Takusagawa F, (2003): Catalytic mechanism of glycine N-methyltransferase. Biochemistry 42: 8394-402.

            Lemieux MJ, Song J, Kim MJ, Huang Y, Villa A, Auer M, Li XD and Wang DN, (2003): Three-dimensional crystallization of the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily. Protein Sci 12: 2748-56.

            Huang Y, Lemieux MJ, Song J, Auer M and Wang DN, (2003): Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 301: 616-20.

            Takata Y, Yamada T, Huang Y, Komoto J, Gomi T, Ogawa H, Fujioka M and Takusagawa F, (2002): Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190. J Biol Chem 277: 22670-6.

            Komoto J, Huang Y, Takata Y, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M and Takusagawa F, (2002): Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. J Mol Biol 320: 223-35.

            Huang Y, Komoto J, Takata Y, Powell DR, Gomi T, Ogawa H, Fujioka M and Takusagawa F, (2002): Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-eritadenine. J Biol Chem 277: 7477-82.

            Komoto J, Huang Y, Gomi T, Ogawa H, Takata Y, Fujioka M and Takusagawa F, (2000): Effects of site-directed mutagenesis on structure and function of recombinant rat liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme. J Biol Chem 275: 32147-56.

            Kim HK, Nam JY, Han MY, Son KH, Choi JD, Kwon BM, Takusagawa HL, Huang Y and Takusagawa F, (2000): Natural and synthetic analogues of actinomycin D as Grb2-SH2 domain blockers. Bioorg Med Chem Lett 10: 1455-7.

            Huang Y, Komoto J, Konishi K, Takata Y, Ogawa H, Gomi T, Fujioka M and Takusagawa F, (2000): Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymes. J Mol Biol 298: 149-62.

            Komoto J, Huang Y, Hu Y, Takata Y, Konishi K, Ogawa H, Gomi T, Fujioka M and Takusagawa F, (1999): Crystallization and preliminary x-ray diffraction studies of guanidinoacetate methyltransferase from rat liver. Acta Crystallogr D Biol Crystallogr 55: 1928-9.

            Hu Y, Komoto J, Huang Y, Gomi T, Ogawa H, Takata Y, Fujioka M and Takusagawa F, (1999): Crystal structure of S-adenosylhomocysteine hydrolase from rat liver. Biochemistry 38: 8323-33.

            Hu TH, Bei L, Huang YF and Shen X, (1999): [The relationship between fMLP induced neutrophil respiratory burst and the apoptosis of neutrophil]. Shi Yan Sheng Wu Xue Bao 32: 359-66.