Crystal structure of a glucose/H+ symporter and its mechanism of action

被引：103

作者：

Iancu, Cristina V. ^{[1
]}

Zamoon, Jamillah ^{[2
]}

Woo, Sang Bum ^{[1
]}

Aleshin, Alexander ^{[3
]}

Choe, Jun-yong ^{[1
]}

机构：

[1] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Biochem & Mol Biol, N Chicago, IL 60064 USA

[2] Kuwait Univ, Fac Sci, Dept Biol Sci, Kuwait 13060, Kuwait

[3] Sanford Burnham Med Res Inst, Dept Infect Dis, La Jolla, CA 92037 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 44期

基金：

美国国家卫生研究院;

关键词：

major facilitator superfamily; membrane protein; GLUT; sugar transporter; solute-carrier; 2A; ISOLATED MEMBRANE-VESICLES; ESCHERICHIA-COLI; TRANSPORT PROTEIN; GLUT1; INHIBITION; SITE; DEHYDROGENASE; EXPRESSION; MUTATIONS; GRADIENT;

D O I：

10.1073/pnas.1311485110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glucose transporters are required to bring glucose into cells, where it is an essential energy source and precursor in protein and lipid synthesis. These transporters are involved in important common diseases such as cancer and diabetes. Here, we report the crystal structure of the Staphylococcus epidermidis glucose/H+ symporter in an inward-facing conformation at 3.2-angstrom resolution. The Staphylococcus epidermidis glucose/H+ symporter is homologous to human glucose transporters, is very specific and has high avidity for glucose, and is inhibited by the human glucose transport inhibitors cytochalasin B, phloretin, and forskolin. On the basis of the crystal structure in conjunction with mutagenesis and functional studies, we propose a mechanism for glucose/H+ symport and discuss the symport mechanism versus facilitated diffusion.

引用

页码：17862 / 17867

页数：6

共 47 条

[1] Structure and mechanism of the lactose permease of Escherichia coli [J].

Abramson, J ;

Smirnova, I ;

Kasho, V ;

Verner, G ;

Kaback, HR ;

Iwata, S .

SCIENCE, 2003, 301 (5633) :610-615

[2] Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures for biological macromolecules [J].

Adams, Paul D. ;

Mustyakimov, Marat ;

Afonine, Pavel V. ;

Langan, Paul .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2009, 65 :567-573

[3] Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer therapeutics [J].

Airley, Rachel E. ;

Mobasheri, Ali .

CHEMOTHERAPY, 2007, 53 (04) :233-256

[4] Characterisation of new intracellular membranes in Escherichia coli accompanying large scale over-production of the b subunit of F1Fo ATP synthase [J].

Arechaga, I ;

Miroux, B ;

Karrasch, S ;

Huijbregts, R ;

de Kruijff, B ;

Runswick, MJ ;

Walker, JE .

FEBS LETTERS, 2000, 482 (03) :215-219

[5] INHIBITION OF GLUCOSE TRANSPORT IN HUMAN ERYTHROCYTE BY CYTOCHALASIN-B [J].

BLOCH, R .

BIOCHEMISTRY, 1973, 12 (23) :4799-4801

[6] CHARACTERIZATION OF SITE-DIRECTED MUTANTS IN THE LAC PERMEASE OF ESCHERICHIA-COLI .2. GLUTAMATE-325 REPLACEMENTS [J].

CARRASCO, N ;

PUTTNER, IB ;

ANTES, LM ;

LEE, JA ;

LARIGAN, JD ;

LOLKEMA, JS ;

ROEPE, PD ;

KABACK, HR .

BIOCHEMISTRY, 1989, 28 (06) :2533-2539

[7] Structure of a fucose transporter in an outward-open conformation [J].

Dang, Shangyu ;

Sun, Linfeng ;

Huang, Yongjian ;

Lu, Feiran ;

Liu, Yufeng ;

Gong, Haipeng ;

Wang, Jiawei ;

Yan, Nieng .

NATURE, 2010, 467 (7316) :734-U130

[8] Features and development of Coot [J].

Emsley, P. ;

Lohkamp, B. ;

Scott, W. G. ;

Cowtan, K. .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 :486-501

[9] Membrane reconstitution of ABC transporters and assays of translocator function [J].

Geertsma, Eric R. ;

Mahmood, N. A. B. Nik ;

Schuurman-Wolters, Gea K. ;

Poolman, Bert .

NATURE PROTOCOLS, 2008, 3 (02) :256-266

[10]

HASHIRAMOTO M, 1992, J BIOL CHEM, V267, P17502

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