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PR00311

Identifier
BLEOMYCINRST  [View Relations]  [View Alignment]  
Accession
PR00311
No. of Motifs
3
Creation Date
07-FEB-1994  (UPDATE 13-JUN-1999)
Title
Bleomycin resistance protein signature
Database References

INTERPRO; IPR000335
Literature References
1. SIKIC, B.A., ROSENCWEIG, M. AND CARTER, S.K.
Bleomycin chemotherapy.
ACADEMIC PRESS, NEW YORK.
 
2. DUMAS, P., BERGDOLL, M., CAGNON, C. AND MASSON, J-M.
Crystal structure and site-directed mutagenesis of a bleomycin
resistance protein and their significance for drug sequestering.
EMBO J. 13(11) 2483-2492 (1994).

Documentation
Bleomycin (Blm) is a glycopeptide antibiotic produced naturally by 
actinomycetes. It is a strong DNA-cutting agent and thus finds use as 
a potent anti-cancer drug [1]. The DNA-cutting mechanism is complex, 
involving concomitant oxidation of FeII and reduction of oxygen. In
addition to iron, Blm binds other transition metals: cobalt, nickel, 
copper and zinc. Actinomycetes have developed a defence mechanism 
against this lethal compound, producing a protein that confers 
resistance to Blm through drug sequestering.
 
The crystal structure of the bleomycin resistance protein reveals 2
identically-folded halves, each having an alpha/beta fold but showing no
sequence similarity [2]. Each half comprises a 4-stranded beta-sheet and
a short alpha-helix (3 turns). The sheets within each half lie roughly at
right-angles and are related by an approximate 2-fold axis. The crystal
packing shows compact dimers that have a hydrophobic interface and are
involved in mutual chain exchange. 
 
BLEOMYCINRST is a 3-element fingerprint that provides a signature for
bleomycin resistance proteins. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from short conserved
regions in the first of the alpha/beta folds. Two iterations on OWL25.1
were required to reach convergence, at which point a true set comprising
7 sequences was identified. 
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3666
2000
123
True Positives
BLE1_BACSP    BLE2_STAAU    BLE_KLEPN     BLE_STRHI     
Q53793 Q56158
Sequence Titles
BLE1_BACSP  BLEOMYCIN RESISTANCE PROTEIN (BRP) - BACILLUS SP., AND STAPHYLOCOCCUS AUREUS. 
BLE2_STAAU BLEOMYCIN RESISTANCE PROTEIN - STAPHYLOCOCCUS AUREUS.
BLE_KLEPN BLEOMYCIN RESISTANCE PROTEIN (BRP) (CL990 RESISTANCE PROTEIN) - KLEBSIELLA PNEUMONIAE.
BLE_STRHI BLEOMYCIN RESISTANCE PROTEIN (BRP) (PHLEOMYCIN RESISTANCE PROTEIN) - STREPTOALLOTEICHUS HINDUSTANUS.
Q53793 BLEOMYCIN/PHLEOMYCIN BINDING PROTEIN - STREPTOMYCES VERTICILLUS.
Q56158 PHLEOMYCIN/BLEOMYCIN BINDING PROTEIN - STREPTOMYCES VERTICILLUS.
Scan History
OWL25_1    2  100  NSINGLE    
OWL26_0 1 100 NSINGLE
SPTR37_9f 2 100 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
QSIPALPVGDIKKSIGFY BLE1_BACSP 3 3 -
QSIPALPVGDIKKSIGFY BLE2_STAAU 5 5 -
SAVPVLTARDVAGAVEFW BLE_STRHI 6 6 -
QATPNLPSRDFDSTAAFY BLE_KLEPN 4 4 -

Motif 2 width=12
Element Seqn Id St Int Rpt
DKLGFTLVHHED BLE1_BACSP 22 1 -
DKVGFTLVHHED BLE2_STAAU 24 1 -
DRLGFSRDFVED BLE_STRHI 25 1 -
ERLGFGIVFRDA BLE_KLEPN 22 0 -

Motif 3 width=12
Element Seqn Id St Int Rpt
GFAVLMCNEVRI BLE1_BACSP 34 0 -
GFAVLMCNEVRI BLE2_STAAU 36 0 -
DFAGVVRDDVTL BLE_STRHI 37 0 -
GWMILQRGDLML BLE_KLEPN 34 0 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
QSIPALPVGDIKKSIGFY BLE1_BACSP 3 3 -
QSIPALPVGDIKKSIGFY BLE2_STAAU 5 5 -
GAIPVLTAVDVPAGVAFW Q56158 6 6 -
SAVPVLTARDVAGAVEFW BLE_STRHI 6 6 -
QATPNLPSRDFDSTAAFY BLE_KLEPN 4 4 -
GAVPVLTAVDVPANVSFW Q53793 6 6 -

Motif 2 width=12
Element Seqn Id St Int Rpt
DKLGFTLVHHED BLE1_BACSP 22 1 -
DKVGFTLVHHED BLE2_STAAU 24 1 -
GTLGFEEDFADD Q56158 25 1 -
DRLGFSRDFVED BLE_STRHI 25 1 -
ERLGFGIVFRDA BLE_KLEPN 22 0 -
DTLGFEKDFGDR Q53793 25 1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
GFAVLMCNEVRI BLE1_BACSP 34 0 -
GFAVLMCNEVRI BLE2_STAAU 36 0 -
GFAGIHRGDVQL Q56158 37 0 -
DFAGVVRDDVTL BLE_STRHI 37 0 -
GWMILQRGDLML BLE_KLEPN 34 0 -
DFAGVRRGDIRL Q53793 37 0 -