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PR01266

Identifier
GSTRNSFRASEA  [View Relations]  [View Alignment]  
Accession
PR01266
No. of Motifs
4
Creation Date
21-DEC-1999
Title
Alpha-class glutathione S-transferase signature
Database References

PDB; 1GSD
SCOP; 1GSD
CATH; 1GSD
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.BIOCHEMISTRY 220 645-661 (1994).

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 phenomenom 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].
 
Alpha-class GSTs show substrate specificity for cumene hydroperoxide (CuOOH)
and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-C1), amongst others. In 
addition, this class exhibits a number of differences from the
characteristic GST structure: within domain II, there is a short 3-residue
beta-strand near the C-terminal segment and a longer alpha-7 helix (due to
insertions at the N-terminus and near to the middle of this helix); domain I
is formed from two separate segments of the sequence. This occurs because
an extra helix (alpha-11) formed via folding of the C-terminal region of the
polypeptide chain is also part of this domain [3]. This helix covers the
substrate bound in the H subsite, which is thought to explain the preference
of alpha class GSTs for more hydrophobic compounds [1]. 
 
GSTRNSFRASEA is a 4-element fingerprint that provides a signature for alpha-
class glutathione S-transferases. The fingerprint was derived from an
initial alignment of 10 sequences: the motifs were drawn from conserved
regions spanning the full alignment length - motif 1 spans alpha-helix 1; 
motif 2 includes the N-terminal region of helix 4 and the preceding loop; 
motif 3 spans helix 7 and the N-terminal region of the following loop; and 
motif 4 includes helix 11 and the C-terminal loop. Two iterations on 
SPTR37_10f were required to reach convergence, at which point a true set
comprising 24 sequences was identified. 
Summary Information
24 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
424242424
30000
20000
1234
True Positives
GTA1_ANTST    GTA1_BOVIN    GTA1_CHICK    GTA1_HUMAN    
GTA1_MOUSE GTA1_PIG GTA1_RABIT GTA1_RAT
GTA2_HUMAN GTA2_MOUSE GTA2_RAT GTA3_CHICK
GTA3_HUMAN GTA3_RAT GTA4_HUMAN GTA4_MOUSE
GTC1_RAT GTC2_RAT GTC_MOUSE GTC_RABIT
O18879 P70686 Q12760 Q29057
Sequence Titles
GTA1_ANTST  GLUTATHIONE S-TRANSFERASE (EC 2.5.1.18) (GST CLASS-ALPHA) - ANTECHINUS STUARTII  
GTA1_BOVIN GLUTATHIONE S-TRANSFERASE ALPHA (EC 2.5.1.18) (GST CLASS-ALPHA) - BOS TAURUS (BO
GTA1_CHICK GLUTATHIONE S-TRANSFERASE (EC 2.5.1.18) (GST CLASS-ALPHA) - GALLUS GALLUS (CHICK
GTA1_HUMAN GLUTATHIONE S-TRANSFERASE A1 (EC 2.5.1.18) (GTH1) (HA SUBUNIT 1) (GST-EPSILON) (
GTA1_MOUSE GLUTATHIONE S-TRANSFERASE YA CHAIN (EC 2.5.1.18) (GST CLASS-ALPHA) - MUS MUSCULU
GTA1_PIG GLUTATHIONE S-TRANSFERASE ALPHA M14 (EC 2.5.1.18) (GST CLASS-ALPHA) - SUS SCROFA
GTA1_RABIT GLUTATHIONE S-TRANSFERASE ALPHA I (EC 2.5.1.18) (GSTA1-1) (GST CLASS- ALPHA) - O
GTA1_RAT GLUTATHIONE S-TRANSFERASE YA (EC 2.5.1.18) (LIGANDIN) (CHAIN 1) (GST CLASS-ALPHA
GTA2_HUMAN GLUTATHIONE S-TRANSFERASE A2 (EC 2.5.1.18) (GTH2) (HA SUBUNIT 2) (GST- GAMMA) (G
GTA2_MOUSE GLUTATHIONE S-TRANSFERASE GT41A (EC 2.5.1.18) (GST CLASS-ALPHA) - MUS MUSCULUS (
GTA2_RAT GLUTATHIONE S-TRANSFERASE YA (EC 2.5.1.18) (LIGANDIN) (CHAIN 1) (GST CLASS-ALPHA
GTA3_CHICK GLUTATHIONE S-TRANSFERASE 3 (EC 2.5.1.18) (GST-CL3) (GST CLASS-ALPHA) - GALLUS G
GTA3_HUMAN GLUTATHIONE S-TRANSFERASE A3-3 (EC 2.5.1.18) (GST CLASS-ALPHA) - HOMO SAPIENS (H
GTA3_RAT GLUTATHIONE S-TRANSFERASE 8 (EC 2.5.1.18) (GST 8-8) (CHAIN 8) (GST CLASS-ALPHA)
GTA4_HUMAN GLUTATHIONE S-TRANSFERASE A4-4 (EC 2.5.1.18) (GST CLASS-ALPHA) - HOMO SAPIENS (H
GTA4_MOUSE GLUTATHIONE S-TRANSFERASE 5.7 (EC 2.5.1.18) (GST 5.7) (GST CLASS- ALPHA) (GST A4
GTC1_RAT GLUTATHIONE S-TRANSFERASE YC-1 (EC 2.5.1.18) (CHAIN 2) (GST YC1) (GST CLASS-ALPH
GTC2_RAT GLUTATHIONE S-TRANSFERASE YC-2 (EC 2.5.1.18) (CHAIN 2) (GST YC2) (GST CLASS-ALPH
GTC_MOUSE GLUTATHIONE S-TRANSFERASE YC (EC 2.5.1.18) (GST CLASS-ALPHA) - MUS MUSCULUS (MOU
GTC_RABIT GLUTATHIONE S-TRANSFERASE YC (EC 2.5.1.18) (ALPHA II) (GST CLASS- ALPHA) - ORYCT
O18879 GLUTATHIONE-S-TRANSFERASE ISOFORM 2 - BOS TAURUS (BOVINE).
P70686 GLUTATHIONE S-TRANSFERASE (EC 2.5.1.18) (GLUTATHIONE TRANSFERASE) (GLUTATHIONE S
Q12760 GLUTATHIONE S-TRANSFERASE - HOMO SAPIENS (HUMAN).
Q29057 GLUTATHIONE S-TRANSFERASE - SUS SCROFA (PIG).
Scan History
SPTR37_10f 2  80   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RMECIRWLLAAAGVE GTA1_MOUSE 14 14 -
RMECIRWLLAAAGVE GTA2_MOUSE 14 14 -
RMECIRWLLAAAGVE GTA2_RAT 14 14 -
RMECIRWLLAAAGVE GTA1_RAT 14 14 -
RMESTRWLLAAAGVE GTA1_HUMAN 14 14 -
RMESIRWLLAAAGVE GTA2_HUMAN 14 14 -
RMEPIRWLLAAAGVE GTA3_HUMAN 15 15 -
RMESIRWLLAAAGVE GTA4_MOUSE 15 15 -
RMESIRWLLATAGVE GTA3_RAT 15 15 -
RMESVRWVLAAAGVE GTA4_HUMAN 15 15 -

Motif 2 width=17
Element Seqn Id St Int Rpt
YGKDMKERALIDMYSEG GTA1_MOUSE 81 52 -
YGKDMKERALIDMYTEG GTA2_MOUSE 81 52 -
YGKDMKERALIDMYSEG GTA2_RAT 81 52 -
YGKDMKERALIDMYTEG GTA1_RAT 81 52 -
YGKDIKERALIDMYIEG GTA1_HUMAN 81 52 -
YGKDIKEKALIDMYIEG GTA2_HUMAN 81 52 -
YGKDIKERALIDMYTEG GTA3_HUMAN 82 52 -
YGKDLKERVRIDMYADG GTA4_MOUSE 82 52 -
YGKDLKERVRIDMYADG GTA3_RAT 82 52 -
FGKNLKERTLIDMYVEG GTA4_HUMAN 82 52 -

Motif 3 width=15
Element Seqn Id St Int Rpt
PAFEKVLKSHGQDYL GTA1_MOUSE 133 35 -
PAFEKVLKSHGQDYL GTA2_MOUSE 133 35 -
PAFEKVLKSHGQDYL GTA2_RAT 133 35 -
PAFEKVLKSHGQDYL GTA1_RAT 133 35 -
PAFEKVLKSHGQDYL GTA1_HUMAN 133 35 -
PAFEKVLKSHGQDYL GTA2_HUMAN 133 35 -
PAFEKVLQSHGQDYL GTA3_HUMAN 134 35 -
PVFEKILKDHGEAFL GTA4_MOUSE 134 35 -
PVFEKILKDHGEAFL GTA3_RAT 134 35 -
PVFEKILRGHGQSFL GTA4_HUMAN 134 35 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PNVKKFLQPGSQRKPPMD GTA1_MOUSE 191 43 -
PNVKKFLQPGSQRKPPLD GTA2_MOUSE 191 43 -
PNVKKFLQPGSQRKPAMD GTA2_RAT 191 43 -
PNVKKFLQPGSQRKLPMD GTA1_RAT 191 43 -
PTVKKFLQPGSPRKPPMD GTA1_HUMAN 191 43 -
PTVKKFLQPGSPRKPPMD GTA2_HUMAN 191 43 -
PTVKKFLQPGSPRKPPAD GTA3_HUMAN 192 43 -
PTIKKFLQPGSQRKPPPD GTA4_MOUSE 192 43 -
PTIKKFLQPGSQRKPPPD GTA3_RAT 192 43 -
PTIKRFLEPGSKKKPPPD GTA4_HUMAN 192 43 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RMECIRWLLAAAGVE GTA1_PIG 14 14 -
RMECIRWLLAAAGVE GTA1_MOUSE 14 14 -
RMECIRWLLAAAGVE Q29057 15 15 -
RMECIRWLLAAAGVE GTA2_MOUSE 14 14 -
RMESIRWLLAAAGEE GTA1_RABIT 15 15 -
RMESIRWLLAAAGVE Q12760 15 15 -
RMEPIRWLLAAAGVE GTC1_RAT 14 14 -
RMECIRWLLAAAGVE GTA2_RAT 14 14 -
RMECIRWLLAAAGVE GTA1_RAT 14 14 -
RMECIRWLLAAAGVE O18879 15 15 -
RMEPIRWLLAAAGVE GTC_MOUSE 14 14 -
RMESTRWLLAAAGVE GTA1_HUMAN 14 14 -
RMESIRWLLAAAGVE GTA2_HUMAN 14 14 -
RMEPIRWLLAAAGVE GTC2_RAT 14 14 -
RMECIRWLLAAAGVE GTA1_BOVIN 14 14 -
RMEPIRWLLAAAGVE GTA3_HUMAN 15 15 -
RMESIRWLLTAAGVE GTC_RABIT 14 14 -
RMEPVRWLLAAAGVE P70686 15 15 -
RMESVRWLLAAAGVE GTA1_CHICK 15 15 -
KMESIRWLLAAAGVE GTA3_CHICK 14 14 -
RMESIRWLLAAAGVE GTA4_MOUSE 15 15 -
RMESIRWLLATAGVE GTA3_RAT 15 15 -
RMEAIRWLLAVAGVE GTA1_ANTST 15 15 -
RMESVRWVLAAAGVE GTA4_HUMAN 15 15 -

Motif 2 width=17
Element Seqn Id St Int Rpt
YGKDAKERALIDMYTEG GTA1_PIG 81 52 -
YGKDMKERALIDMYSEG GTA1_MOUSE 81 52 -
YGKDAKERALIDMYTEG Q29057 82 52 -
YGKDMKERALIDMYTEG GTA2_MOUSE 81 52 -
YGKDMKERALIDMYTEG GTA1_RABIT 82 52 -
YGKDTKERALIDMYIEG Q12760 82 52 -
YGKDMKERALIDMYAEG GTC1_RAT 81 52 -
YGKDMKERALIDMYSEG GTA2_RAT 81 52 -
YGKDMKERALIDMYTEG GTA1_RAT 81 52 -
YGKDMKERALIDMYSEG O18879 81 51 -
YGKDMKERAIIDMYTEG GTC_MOUSE 81 52 -
YGKDIKERALIDMYIEG GTA1_HUMAN 81 52 -
YGKDIKEKALIDMYIEG GTA2_HUMAN 81 52 -
YGKDMKERALIDMYAEG GTC2_RAT 81 52 -
YGKDMKERALIDMYSEG GTA1_BOVIN 81 52 -
YGKDIKERALIDMYTEG GTA3_HUMAN 82 52 -
YGKDIKERALIDMYTEG GTC_RABIT 81 52 -
YGKDMKERALIDMYAEG P70686 82 52 -
YGKDLKERALIDMYVEG GTA1_CHICK 82 52 -
YGKDLKERALIDMYVGG GTA3_CHICK 81 52 -
YGKDLKERVRIDMYADG GTA4_MOUSE 82 52 -
YGKDLKERVRIDMYADG GTA3_RAT 82 52 -
LGKDMKEHAQIIMYSEG GTA1_ANTST 81 51 -
FGKNLKERTLIDMYVEG GTA4_HUMAN 82 52 -

Motif 3 width=15
Element Seqn Id St Int Rpt
PAFEKVLKSHGQDYL GTA1_PIG 133 35 -
PAFEKVLKSHGQDYL GTA1_MOUSE 133 35 -
PAFEKVLKSHGQDYL Q29057 134 35 -
PAFEKVLKSHGQDYL GTA2_MOUSE 133 35 -
PAFEKVLKSHGQDYL GTA1_RABIT 134 35 -
PAFEKVLKSHGQDYL Q12760 134 35 -
PAFEKVLKSHGQDYL GTC1_RAT 133 35 -
PAFEKVLKSHGQDYL GTA2_RAT 133 35 -
PAFEKVLKSHGQDYL GTA1_RAT 133 35 -
PAFEKVLKNHGQDYL O18879 133 35 -
PAFEKVLKSHGQDYL GTC_MOUSE 133 35 -
PAFEKVLKSHGQDYL GTA1_HUMAN 133 35 -
PAFEKVLKSHGQDYL GTA2_HUMAN 133 35 -
PAYEKVLKSHGQDYL GTC2_RAT 133 35 -
PAFENVLKSHGQDYL GTA1_BOVIN 133 35 -
PAFEKVLQSHGQDYL GTA3_HUMAN 134 35 -
PAFEKVLKSHGQDYL GTC_RABIT 133 35 -
PAYEKVLKSHGQDYL P70686 134 35 -
PVFEKVLKDHGHDFL GTA1_CHICK 134 35 -
PAYEKVLKDHGQDFL GTA3_CHICK 133 35 -
PVFEKILKDHGEAFL GTA4_MOUSE 134 35 -
PVFEKILKDHGEAFL GTA3_RAT 134 35 -
PAFENVLKTHGQNFL GTA1_ANTST 133 35 -
PVFEKILRGHGQSFL GTA4_HUMAN 134 35 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PTVKKFLQPGSQRKPPMD GTA1_PIG 191 43 -
PNVKKFLQPGSQRKPPMD GTA1_MOUSE 191 43 -
PTVKKFLQPGSQRKPPTD Q29057 192 43 -
PNVKKFLQPGSQRKPPLD GTA2_MOUSE 191 43 -
PTVKKFLQPGSQRKPPMD GTA1_RABIT 192 43 -
PTVKKFLQPGSPRKPPMD Q12760 192 43 -
PTVKKFLQPGSQRKPLED GTC1_RAT 191 43 -
PNVKKFLQPGSQRKPAMD GTA2_RAT 191 43 -
PNVKKFLQPGSQRKLPMD GTA1_RAT 191 43 -
PAVKKFLQPGSQRKPPMD O18879 191 43 -
PTVKKFLQPGSQRKPFDD GTC_MOUSE 191 43 -
PTVKKFLQPGSPRKPPMD GTA1_HUMAN 191 43 -
PTVKKFLQPGSPRKPPMD GTA2_HUMAN 191 43 -
PTVKKFLQPGSQRKPFDD GTC2_RAT 191 43 -
PAVKKFLQPGSQRKPPTD GTA1_BOVIN 191 43 -
PTVKKFLQPGSPRKPPAD GTA3_HUMAN 192 43 -
PTVKKFLQPGSQRNPPDD GTC_RABIT 191 43 -
PTVKKFLQPGSQRKPYED P70686 192 43 -
PNIKKFLQPGSQRKPRLE GTA1_CHICK 192 43 -
PTIKKFLAPGSKRKPISD GTA3_CHICK 191 43 -
PTIKKFLQPGSQRKPPPD GTA4_MOUSE 192 43 -
PTIKKFLQPGSQRKPPPD GTA3_RAT 192 43 -
PTVKTFLAPGSKRKPVPD GTA1_ANTST 191 43 -
PTIKRFLEPGSKKKPPPD GTA4_HUMAN 192 43 -