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PR01625

Identifier
GSTRNSFRASEO  [View Relations]  [View Alignment]  
Accession
PR01625
No. of Motifs
3
Creation Date
17-DEC-2001
Title
Omega-class glutathione S-transferase signature
Database References

PDB; 1EEM
SCOP; 1EEM
CATH; 1EEM
Literature References
1. ALLARDYCE, C.S., MCDONAGH, P.D., LIAN, L-Y., WOLF, R. AND ROBERTS, G.C.K.
The role of tyrosine-9 and the C-terminal helix in the catalytic mechanism
of alpha-class glutathione S-transferases.
BIOCHEM.J. 343 525-531 (1999).
 
2. NUCCETELLI, M.N., MAZZETTI, A.P., ROSSJOHN, J., PARKER, M.W., BOARD, P.,
CACCURI, A.M., FEDERICI, G., RICCI, G. AND LO BELLO, M.
Shifting substrate specificity of human glutathione transferase (from class
pi to class alpha) by a single point mutation.
BIOCHEM.BIOPHYS.RES.COMMUN. 252(1) 184-189 (1998).
 
3. DIRR, H., REINEMER, P. AND HUBER, R.
X-ray crystal structures of cytosolic glutathione S-transferases.
Implications for protein architecture, substrate recognition and catalytic
function.
EUR.J.BIOCHEM. 220 645-661 (1994).
 
4. BOARD, P.G., COGGAN, M., CHELVANAYAGAM, G., EASTEAL, S., JERMIIN, L.S.,
SCHULTE, G.K., DANLEY, D.E., HOTH, L.R., GRIFFOR, M.C., KAMATH, A.V.,
ROSNER, M.H., CHRUNYK, B.A., PERREGAUX, D.E., GABEL, C.A., GEOGHEGAN, K.F.
AND PANDIT, J.
Identification, characterization and crystal structure of the omega class
glutathione transferases.
J.BIOL.CHEM. 275(32) 24798-24806 (2000).

Documentation
Glutathione S-transferases (GSTs) are a range of dimeric proteins that
catalyse the conjugation of glutathione to a wide range of hydrophobic
compounds through the formation of a thioether bond with their
electrophilic centre. Based on amino acid sequence identity, there are at
least seven major classes of GST (designated alpha, kappa, mu, pi, sigma, 
theta and zeta). Pi-, mu-, alpha- and theta-class crystal structures have
been elucidated; all possess a similar GSH-binding site (G subsite), but 
the hydrophobic substrate-binding site (H subsite) is subject to variation 
across the classes [1]. Whilst most of the GSTs share common substrates,
there are distinct differences in substrate preference between subfamilies.
Sequence similarity between classes is rather low, ranging between 20-30%.
However, a single point mutation in the H-subsite region is enough to shift
substrate specificity from class pi to alpha [2].
 
These enzymes have evolved as a cellular protection system against a range
of xenobiotics, oxidative metabolism by-products, and in particular are
known to metabolise a number of environmental carcinogens. The wide range
of GST isoforms present in the various subfamilies provides cells with an
efficient way of scavenging the huge number of potentially toxic compounds
encountered. Genetic differences in GST expression have been implicated in
individual susceptibility to certain types of cancer. Conversely, over- 
expression of GSTs is thought to be involved in the phenomenon of multi-drug
resistance to cancer chemotherapy.
 
In spite of relatively low sequence identity, the GSTs exhibit a high degree
of structural similarity. The structure comprises 2 domains: domain I is the
smaller of the two and is formed from the N-terminal region of the sequence
- it possesses an alpha/beta-type core structure comprising a central 
4-stranded beta-pleated sheet, flanked on one side by two alpha-helices and
on the other by a single helix; domain II is the larger of the domains and
occurs towards the C-terminal region of the sequence - it contains a
predominantly all-alpha-type core comprising 5 amphipathic alpha-helices,
arranged in a right-handed spiral. The active site is situated near the
subunit interface. G-subsite molecular recognition is attributable mostly 
to residues in domain I of one subunit and 1 or 2 residues in domain II of
the other subunit. Residues contributing to H-subsite specificity are found
within domains I and II of the same subunit [3].
 
Recently, a new class of GST has been discovered by analysis of expressed
sequence tag databases, termed the omega-class. Recombinant human omega-
class GST shows glutathione-dependent thiol transferase and dehydroascorbate
reduction activity. This sort of activity has not been observed in any other
class of GSTs, but is associated with the glutaredoxins (thioltransferases).
Members of this class of GST have a novel unique N-terminal extension, and a
cysteine residue in the active site, which is different from the tyrosine
and serine residues found at the active sites of other eukaryotic GSTs [4].
 
GSTRNSFRASEO is a 3-element fingerprint that provides a signature for
omega-class glutathione S-transferases. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length - motif 1 includes
strand 1; motif 2 encompasses the loop between helices 3 and 4, and the
N-terminal portion of helix 4; and motif 3 encodes the loop between helices
6 and 7, and the N-terminal half of helix 7. Two iterations on SPTR40_18f
were required to reach convergence, at which point a true set comprising 15
sequences was identified. A single partial match was also found, YKJ3_CAEEL,
a C.elegans chromosome III hypothetical protein that exhibits a high degree
of similarity to omega-class GSTs, but fails to make a significant match 
with motif 1.
Summary Information
  15 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3151515
2011
123
True Positives
GTO1_HUMAN    GTO1_MOUSE    GTO1_PIG      GTO1_RAT      
O17234 O45352 Q9D2J1 Q9D2S1
Q9H4Y5 Q9VSL2 Q9VSL3 Q9VSL4
Q9VSL5 Q9VSL6 YK67_CAEEL
True Positive Partials
Codes involving 2 elements
YKJ3_CAEEL
Sequence Titles
GTO1_HUMAN  Glutathione transferase omega 1 (EC 2.5.1.18) (GSTO 1-1) - Homo sapiens (Human). 
GTO1_MOUSE Glutathione transferase omega 1 (EC 2.5.1.18) (GSTO 1-1) - Mus musculus (Mouse).
GTO1_PIG Glutathione transferase omega 1 (EC 2.5.1.18) (GSTO 1-1) (Glutathione- dependent dehydroascorbate reductase) - Sus scrofa (Pig).
GTO1_RAT Glutathione transferase omega 1 (EC 2.5.1.18) (GSTO 1-1) (Glutathione- dependent dehydroascorbate reductase) - Rattus norvegicus (Rat).
O17234 K10F12.4 PROTEIN - Caenorhabditis elegans.
O45352 F13A7.10 PROTEIN - Caenorhabditis elegans.
Q9D2J1 4930425C18RIK PROTEIN - Mus musculus (Mouse).
Q9D2S1 1700020F09RIK PROTEIN - Mus musculus (Mouse).
Q9H4Y5 BA127L20.1 (NOVEL GLUTATHIONE-S-TRANSFERASE) - Homo sapiens (Human).
Q9VSL2 CG6776 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VSL3 CG6781 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VSL4 CG6673 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VSL5 CG6673 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VSL6 CG6662 PROTEIN - Drosophila melanogaster (Fruit fly).
YK67_CAEEL Hypothetical 28.5 kDa protein C29E4.7 in chromosome III - Caenorhabditis elegans.

YKJ3_CAEEL Hypothetical 42.8 kDa protein C02D5.3 in chromosome III - Caenorhabditis elegans.
Scan History
SPTR40_18f 2  20   NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GSIRIYSMRFCPFAER GTO1_HUMAN 22 22 -
GLIRVYSMRFCPFAQR GTO1_PIG 22 22 -
GVLRLYSMRFCPYAQR Q9VSL2 20 20 -
GSFRVYNMRFCPWAER YK67_CAEEL 23 23 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YPGKKLLPDDPYEKA GTO1_HUMAN 97 59 -
YPGKKLLPDDPYEKA GTO1_PIG 97 59 -
YPENPLLPKDPLKRA Q9VSL2 98 62 -
FPETRILPTDPYEKV YK67_CAEEL 97 58 -

Motif 3 width=20
Element Seqn Id St Int Rpt
FFGGNSISMIDYLIWPWFER GTO1_HUMAN 164 52 -
YFGGSSLSMIDYLIWPWFER GTO1_PIG 164 52 -
YFGGNKPGFVDYMIWPWFER Q9VSL2 159 46 -
FYAGSQPGYPDYLSFPFFEK YK67_CAEEL 162 50 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GSIRIYSMRFCPFAER GTO1_HUMAN 22 22 -
GLIRVYSMRFCPFAQR GTO1_PIG 22 22 -
GQIRVYSMRFCPFAQR GTO1_RAT 22 22 -
GVIRIYSMRFCPYSHR Q9D2S1 22 22 -
GLIRIYSMRFCPYSHR Q9H4Y5 22 22 -
GVIRIYSMRFCPYSHR Q9D2J1 22 22 -
GQIRVYSMRFCPFAQR GTO1_MOUSE 22 22 -
GVLRLYSMRFCPYAQR Q9VSL2 20 20 -
GVLRYYSMRFCPYSQR Q9VSL4 21 21 -
GILRLYSMRFCPFAQR Q9VSL3 20 20 -
GILKLYSMRFCPYAHR Q9VSL6 20 20 -
GVPRFFSMAFCPFSHR Q9VSL5 21 21 -
GNYRLYSMRFCPYAQR O17234 97 97 -
NTFRIYSMRFCPAAQR O45352 37 37 -
GSFRVYNMRFCPWAER YK67_CAEEL 23 23 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YPGKKLLPDDPYEKA GTO1_HUMAN 97 59 -
YPGKKLLPDDPYEKA GTO1_PIG 97 59 -
YPEKKLFPDDPYEKA GTO1_RAT 97 59 -
YPGRKLFPYDPYERA Q9D2S1 97 59 -
YPGRKLFPYDPYERA Q9H4Y5 97 59 -
YPGRKLFPYDPYERA Q9D2J1 97 59 -
YPEKKLFPDDPYKKA GTO1_MOUSE 97 59 -
YPENPLLPKDPLKRA Q9VSL2 98 62 -
YPQTRLFPTDPLQKA Q9VSL4 315 278 -
YPLRPLYPRDPLKKV Q9VSL3 98 62 -
YPEVPLYPKDLLKKA Q9VSL6 98 62 -
YPQTRLFPTDPLQKA Q9VSL5 99 62 -
FPTNTILPRDAYEKA O17234 171 58 -
FPETKILPSDPYEKV O45352 113 60 -
FPETRILPTDPYEKV YK67_CAEEL 97 58 -

Motif 3 width=20
Element Seqn Id St Int Rpt
FFGGNSISMIDYLIWPWFER GTO1_HUMAN 164 52 -
YFGGSSLSMIDYLIWPWFER GTO1_PIG 164 52 -
FFGGNSLSMIDYLIWPWFQR GTO1_RAT 164 52 -
FFGGDCISMIDYLVWPWFER Q9D2S1 165 53 -
FFGGTCISMIDYLLWPWFER Q9H4Y5 165 53 -
LFGGDCISMIDYLVWPWFER Q9D2J1 165 53 -
FLGGDSPSMVDYLTWPWFQR GTO1_MOUSE 163 51 -
YFGGNKPGFVDYMIWPWFER Q9VSL2 159 46 -
YFAGQHIGIVDYMIWPWFER Q9VSL4 381 51 -
FFGGEQTGILDYMIWPWCER Q9VSL3 158 45 -
FFGGDSPGMLDYMMWPWCER Q9VSL6 163 50 -
YFAGQHIGIVDYMIWPWFER Q9VSL5 165 51 -
FYGGRQPGYADYLMWPFLER O17234 236 50 -
YSGTSSPGFVDYLIYPSFQR O45352 180 52 -
FYAGSQPGYPDYLSFPFFEK YK67_CAEEL 162 50 -