TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


2.A.1.5.1
β- and α-galactopyranoside:H+ symporter, LacY. Transports lactose, melibiose, thio-β-methyl galactopyranoside (TMG), isopropyl-β-thiogalactoside (IPTG), 4-nitrophenyl-beta-D-galactopyranoside, 4-nitrophenyl-alpha-D-galactopyranoside and galactopyranosyl-1-glycerol. Single point mutations allow transport of sucrose and maltose (King and Wilson 1990).  Crystal structures and modeling reveal the cytoplasmic open state and the periplasmic open state (PDB ID: 1PV7). A structure with a bound lactose homolog, beta-D-galactopyranosyl-1-thio-beta-D-galactopyranoside, revealed the sugar-binding site in a cavity, and residues that play major roles in substrate recognition and proton translocation were identified (Abramson et al., 2003Pendse et al., 2010). The membrane lipid composition determines the topology of LacY (Dowhan and Bogdanov, 2011). Smirnova et al. (2011) have provided evidence that the opening of the periplasmic cavity in LacY is the limiting step for sugar binding. Evidence for an alternating sites mechanism of transport has been summarized (Smirnova et al., 2011). Eames and Kortemme (2012) have shown that when considering expression of the lac operon, LacY function (H+ co-transport) and not protein production is the primary origin of cost fitness. Homology threading of several MFS porters based on the LacY 3-d structure has been reported (Kasho et al., 2006). The alternating-access mechanism has been suggested to arise from inverted topological repeats (Radestock and Forrest, 2011; Madej et al. 2012), but this proposal has been contested (Västermark and Saier 2014; Västermark et al. 2014). Mechanistic features of LacY have been summarized (Kaback 2015). Insertion into the membrane depends on YidC (TC# 2.A.9.3.1) and may occur in a stepwise, stochastic manner employing multiple coexisting pathways to complete the folding process (Serdiuk et al. 2017). The glucose Enzyme IIA (Crr) protein binds LacY to allosterically inhibit its activity, promoting inducer exclusion (Hoischen et al. 1996; Hariharan et al. 2015). Protonated LacY binds D-galactopyranosides specifically, inducing an occluded state that can open to either side of the membrane (Kumar et al. 2014). LacY can form amyloid-like fibrils under destabilizing conditions (Stroobants et al. 2017).

Accession Number:P02920
Protein Name:LacY aka B0343
Length:417
Molecular Weight:46503.00
Species:Escherichia coli [83333]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate 4-nitrophenyl-beta-D-galactopyranoside, 4-nitrophenyl-alpha-D-galactopyranoside, methyl-beta-thiogalactoside, beta-galactopyranosyl-1-glycerol, methyl-beta-D-galactoside, D-melibiose, isopropyl beta-thiogalactoside, beta-galactosides, Alpha-galactosides, D-sucrose, D-maltose, D-lactose

Cross database links:

Genevestigator: P02920
EchoBASE: EB0521
EcoGene: EG10526
eggNOG: COG0477
HEGENOM: HBG337116
DIP: DIP-10080N
RefSeq: AP_000995.1    NP_414877.1   
Entrez Gene ID: 949083   
Drugbank: Drugbank Link   
BioCyc: EcoCyc:LACY-MONOMER    ECOL168927:B0343-MONOMER   
KEGG: ecj:JW0334    eco:b0343   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0030395 F:lactose binding
GO:0015528 F:lactose:hydrogen symporter activity
GO:0015767 P:lactose transport

References (12)

[1] “Sequence of the lactose permease gene.”  Buechel D.E.et.al.   6444453
[2] “The complete genome sequence of Escherichia coli K-12.”  Blattner F.R.et.al.   9278503
[3] “Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.”  Hayashi K.et.al.   16738553
[4] “The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology.”  von Heijne G.et.al.   16453726
[5] “lac permease of Escherichia coli: topology and sequence elements promoting membrane insertion.”  Calamia J.et.al.   2164211
[6] “Membrane topology of helices VII and XI in the lactose permease of Escherichia coli studied by lacY-phoA fusion analysis and site-directed spectroscopy.”  Ujwal M.L.et.al.   7578103
[7] “The interaction between aspartic acid 237 and lysine 358 in the lactose carrier of Escherichia coli.”  King S.C.et.al.   1848449
[8] “Amino acid substitution in the lactose carrier protein with the use of amber suppressors.”  Huang A.-M.et.al.   1644770
[9] “The lac permease of Escherichia coli: a prototypic energy-transducing membrane protein.”  Kaback H.R.et.al.   2203471
[10] “Toward the bilayer proteome, electrospray ionization-mass spectrometry of large, intact transmembrane proteins.”  Whitelegge J.P.et.al.   10485888
[11] “Global topology analysis of the Escherichia coli inner membrane proteome.”  Daley D.O.et.al.   15919996
[12] “Structure and mechanism of the lactose permease of Escherichia coli.”  Abramson J.et.al.   12893935
Structure:
1M2U   1PV6   1PV7   2CFP   2CFQ   2V8N   2Y5Y   4ZYR   4oaa   5gxb   [...more]

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
Window Size: Angle:  
FASTA formatted sequence
1:	MYYLKNTNFW MFGLFFFFYF FIMGAYFPFF PIWLHDINHI SKSDTGIIFA AISLFSLLFQ 
61:	PLFGLLSDKL GLRKYLLWII TGMLVMFAPF FIFIFGPLLQ YNILVGSIVG GIYLGFCFNA 
121:	GAPAVEAFIE KVSRRSNFEF GRARMFGCVG WALCASIVGI MFTINNQFVF WLGSGCALIL 
181:	AVLLFFAKTD APSSATVANA VGANHSAFSL KLALELFRQP KLWFLSLYVI GVSCTYDVFD 
241:	QQFANFFTSF FATGEQGTRV FGYVTTMGEL LNASIMFFAP LIINRIGGKN ALLLAGTIMS 
301:	VRIIGSSFAT SALEVVILKT LHMFEVPFLL VGCFKYITSQ FEVRFSATIY LVCFCFFKQL 
361:	AMIFMSVLAG NMYESIGFQG AYLVLGLVAL GFTLISVFTL SGPGPLSLLR RQVNEVA