Cell Physiology and Molecular Biophysics
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Lan Guan, M.D., Ph.D.Assistant Professor of Cell Physiology and Molecular Biophysics
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Texas Tech University Health Sciences Center
3601 4th Street, STOP 6551
Lubbock, Texas 79430
Phone: (806) 743-3102
FAX: (806) 743-1512
Email: Lan.Guan@ttuhsc.edu
Research Interests
My laboratory studies X-ray crystal structures and mechanisms of membrane transport. Membrane transport proteins catalyze transport of solute across a cell membrane and play crucial roles in many aspects of cellular function. Many are targets for pharmacologically and toxicologically active substances. Our current focus is on bacterial and human sugar permeases. The laboratory is well equipped with robotic high-throughput equipment specifically for production and crystallization of membrane proteins.
The main projects are:
1) Crystallization of eukaryotic facilitated glucose transporters (Gluts), funded by NIH R21, 2008.
2) Crystallization and X-ray structural determination of the bacterial melibiose permease (MelB).
Two positions for postdoctoral fellows and one position for a technician are available.
Current Publication list:
Articles
Zhou, Y.G., Guan, L., Freites, J.A., Kaback, H.R. (2008) Opening and closing of the periplasmic gate in lactose permease. Proc Natl Acad Sci U S A. 105 (10):3774-3778.
Guan, L., Mirza, O., Verner, G., Iwata, S, and Kaback, H.R. (2007) Structural determination of the wild-type lactose permease. Proc Natl Acad Sci U S A. 104 (39):15294-15298.
Guan, L. & Kaback, H.R. (2007) Site-directed alkylation of cysteine to test solvent accessibility of membrane proteins. Nature protocol2, 2012 -2017.
Orsolya K.*, Guan, L.*, Szepessy, E. Kukor, Z., T�th, M, and Sahin-T�th, M. (2006) Expression of human cationic trypsinogen with an authentic N terminus using inteinmediated splicing in aminopeptidase P (pepP) deficient Escherichia coli. Protein Expr Purif. 48(1):104-11 (*equal contribution).
Mirza, O.*, Guan, L,*, Verner, G., Iwata, S., and Kaback, H.R. (2006) Structural evidence for sugar recognition and mechanism for galactoside/H+ symport in the lactose permease. EMBO J, 25:1177-1183 (*equal contribution).
Guan, L., Smirnova, I., Verner, G., Nagamoni, S. and Kaback, H.R. (2006) Manipulating phospholipids for crystallization of a membrane transport protein. Proc Natl Acad Sci U S A. 103 (6):1723-1726.
Guan, L. and Kaback, H.R. (2004) Binding affinity of lactose permease is not altered by the H+ electrochemical gradient. Proc Natl Acad Sci U S A. 101 (33):12148-12152.
V�zquez-Ibar, J.L., Guan, L. Weinglass, A.B., Verner, G., Gordillo, R. and Kaback, H.R. (2004) Sugar recognition by the lactose permease of Escherichia coli. J Biol Chem. 19;279(47):49214-49221.
V�zquez-Ibar, J.L.*, Guan, L.*, Svrakic, M. and Kaback, H.R. (2003)Exploiting luminescence spectroscopy to elucidate the interaction between sugar and a tryptophan residue in the lactose permease of Escherichia coli. Proc Natl Acad Sci U S A. 100 (22):12706-12711 (*equal contribution).
Ermolova, N., Guan, L. and Kaback, H.R. (2003) Intermolecular thiol cross-linking via loops in the lactose permease of Escherichia coli. Submitted to Proc Natl Acad Sci U S A.100 (18):10187-10192.
Guan, L., Sahin-Toth, M., Kalai, T., Hideg, K., and Kaback, H.R. (2003) Probing the mechanism of a membrane transport protein with affinity inactivators. J.Biol.Chem. 278(12):10541-10648 (cover of JBC).
Guan, L., Hu, Y.L., and Kaback, H.R. (2003) Aromatic stacking in sugar binding site of lactose permease in Escherichia coli. Biochemistry 42(6):1377-1382, (accelerated publication).
Sorgen, P.L., Hu, Y.L., Guan, L., Kaback, R.H., and Girvin, M. (2002) An approach to membrane protein structure without crystals. Proc Natl Acad Sci U S A. 99(22):14037-14040.
Guan, L., Sahin-Toth, M., and Kaback, H.R. (2002) Changing the lactose permease of Escherichia coli into a galactose-specific symporter. Proc Natl Acad Sci U S A. 99(10):6613-6618.
Guan, L., Murphy, F.D., and Kaback, H.R. (2002) Surface-exposed positions in the transmembrane helices of the lactose permease of Escherichia coli determined by intermolecular thiol cross-linking. Proc Natl Acad Sci U S A. 99(6):3475-3480.
Zhang, W., Guan, L., and Kaback, H.R. (2002) Helices VII and X in the lactose permease of Escherichia coli: proximity and ligand-induced distance changes. J Mol Biol. 315(1):53-62.
Guan, L., Weinglass, A.B., and Kaback, H.R. (2001) Helix packing in the lactose permease of Escherichia coli:
localization of helix VI. J Mol Biol. 312(1):69-77.
Guan, L. and Nakae, T. (2001) Identification of essential charged residues in transmembrane segments of the multidrug transporter MexB of Pseudomonas aeruginosa. J Bacteriol. 183(5):1734-1739.
Guan, L., Ehrmann, M., Yoneyama, H., and Nakae, T. (1999) Membrane topology of the xenobiotic-exporting subunit, MexB, of the MexA,B-OprM extrusion pump in Pseudomonas aeruginosa. J Biol Chem. 4(15):10517-10522.
Book Chapter
Guan, L. & Kaback, H.R. (2004) Glucose/Sugar Transport in Bacteria. Encyclopedia of Biological Chemistry, Volume 2. p. 204-207, Elsevier Inc.
Reviews
Guan, L.*& Kaback, H.R.* (2006) Lessons from lactose permease. Annual Review of Biophysics & Biomolecular Structure (35):67-91(*corresponding author).
Nakae, T., Guan, L., Yoneyama, H., Germ, M., and Nakajima, A. (2002) The topological localization of the subunit proteins of the three-component RND-efflux pump, MexAB-OprM in Pseudomonas aeruginosa. Proceedings of SPIE (4625):106-117 (review article).
Guan, L. (1998) Detection and clinical significance of the mechanisms of b-lactam antibiotic resistance in clinically important pathogen. World Notes on Antibiotics. 19:126-129 (review article in Chinese).