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PR01885

Identifier
MACROMOMYCIN  [View Relations]  [View Alignment]  
Accession
PR01885
No. of Motifs
4
Creation Date
27-JUL-2004
Title
Macromomycin family signature
Database References

PFAM; PF00960 Neocarzinostat
PRODOM; PD012709
INTERPRO; IPR002186
PDB; 2MCM
SCOP; 2MCM
CATH; 2MCM
Literature References
1. SAMY, T.S., HAHM, K.S.,MODEST, E.J., LAMPMAN, G.W., KEUTMANN, H.T.,
UMEZAWA, H., HERLIHY, W.C., GIBSON,  B.W., CARR, S.A. AND BIEMANN, K.
Primary structure of macromomycin, an antitumor antibiotic protein.
J.BIOL.CHEM. 258 183-191 (1983).
 
2. VAN ROEY, P. AND BEERMAN, T.A.
Crystal structure analysis of auromomycin apoprotein (macromomycin) shows 
importance of protein side chains to chromophore binding selectivity.
PROC.NATL.ACAD.SCI.U.S.A. 86 6587-6591 (1989).
 
3. TAKASHIMA, H., AMIYA, S. AND KOBAYASHI, Y.
Neocarzinostatin: interaction between the antitumor-active chromophore 
and the carrier protein.
J.BIOCHEM. 109 807-810 (1991).

Documentation
Macromomycin, the apoprotein of the anti-tumour antibiotic auromomycin,
is a single-chain polypeptide of 112 amino-acid residues cross-linked
by two intramolecular disulphide bonds. Comparison of the structures
of macromomycin, actinoxanthin and neocarzinostatin suggests that they
belong to a family of related proteins [1].
 
The 3D structure of macromomycin has been determined to 1.6A resolution
by means of X-ray crystallography [2]. The fold comprises a flattened 7-
stranded anti-parallel beta-barrel and two anti-parallel beta-sheet 
ribbons. The barrel and ribbons define a deep cleft that forms the 
chromophore binding site [2]. Highly specific side chains extend into this 
cleft and may be important to the chromophore-binding specificity. The 
chromophore binds to DNA as a weak intercalator and causes single- and 
double-strand breaks.
 
The solution structure of the closely-related neocarzinostatin, which
has antibiotic activity for Gram-positive bacteria and anti-tumour 
activity for certain mouse tumours, has been determined by NMR-
spectroscopy [3]. A similar beta-barrel fold was revealed for the 
carrier protein, the chromophore being tightly enwrapped and thus 
shielded from exposure to the solvent [3]. A possible mechanism for
exposure or release of the active principle may be via subtle 
environmental changes, such as in pH [3].
 
MACROMOMYCIN is a 4-element fingerprint that provides a signature for
the macromomycin family. 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 encodes beta-
strand 1 and the following beta-turn; motif 2 spans strand 3 and the
preceding turn; motif 3 encodes strand 6 and the preceding turn; and
motif 4 spans strand 8 and its preceding and following beta-turns. 
A single iteration on SPTR41_24f was required to reach convergence,
no further sequences being identified beyond the starting set.
Summary Information
4 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
44444
30000
20000
1234
True Positives
ATXA_STRGL    CAGA_STRGL    MACM_STRMA    NCZS_STRCZ    
Sequence Titles
ATXA_STRGL  Actinoxanthin precursor (AXN) - Streptomyces globisporus. 
CAGA_STRGL Antitumor antibiotic C-1027 apoprotein precursor (C-1027-AG) - Streptomyces globisporus.
MACM_STRMA Macromomycin precursor (MCR) (Auromomycin apoprotein) - Streptomyces macromomyceticus.
NCZS_STRCZ Neocarzinostatin precursor (NCS) (Mitomalcin) (MMC) - Streptomyces carzinostaticus, and Streptomyces malayensis.
Scan History
SPTR41_24f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
APAFSVSPASGLSDGQSVSV CAGA_STRGL 34 34 -
APAFSVSPASGLSDGQSVSV ATXA_STRGL 34 34 -
APTATVTPSSGLSDGTVVKV NCZS_STRCZ 36 36 -
APGVTVTPATGLSNGQTVTV MACM_STRMA 33 33 -

Motif 2 width=16
Element Seqn Id St Int Rpt
GAAAGETYYIAQCAPV CAGA_STRGL 57 3 -
GAAAGETYYIAQCAPV ATXA_STRGL 57 3 -
GLQAGTAYDVGQCAWV NCZS_STRCZ 59 3 -
GLTPGTVYHVGQCAVV MACM_STRMA 56 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
TTDASGAASFSFVVRKSY CAGA_STRGL 87 14 -
TTDASGAASFSFVVRKSY ATXA_STRGL 87 14 -
TADANGSASTSLTVRRSF NCZS_STRCZ 90 15 -
TADAAGKITAQLKVHSSF MACM_STRMA 87 15 -

Motif 4 width=17
Element Seqn Id St Int Rpt
GTPVGSVDCATAACNLG CAGA_STRGL 111 6 -
GTPVGSVDCATDACNLG ATXA_STRGL 111 6 -
GTRWGTVDCTTAACQVG NCZS_STRCZ 114 6 -
GTPWGTVNCKVVSCSAG MACM_STRMA 112 7 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
APAFSVSPASGLSDGQSVSV CAGA_STRGL 34 34 -
APAFSVSPASGLSDGQSVSV ATXA_STRGL 34 34 -
APTATVTPSSGLSDGTVVKV NCZS_STRCZ 36 36 -
APGVTVTPATGLSNGQTVTV MACM_STRMA 33 33 -

Motif 2 width=16
Element Seqn Id St Int Rpt
GAAAGETYYIAQCAPV CAGA_STRGL 57 3 -
GAAAGETYYIAQCAPV ATXA_STRGL 57 3 -
GLQAGTAYDVGQCAWV NCZS_STRCZ 59 3 -
GLTPGTVYHVGQCAVV MACM_STRMA 56 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
TTDASGAASFSFVVRKSY CAGA_STRGL 87 14 -
TTDASGAASFSFVVRKSY ATXA_STRGL 87 14 -
TADANGSASTSLTVRRSF NCZS_STRCZ 90 15 -
TADAAGKITAQLKVHSSF MACM_STRMA 87 15 -

Motif 4 width=17
Element Seqn Id St Int Rpt
GTPVGSVDCATAACNLG CAGA_STRGL 111 6 -
GTPVGSVDCATDACNLG ATXA_STRGL 111 6 -
GTRWGTVDCTTAACQVG NCZS_STRCZ 114 6 -
GTPWGTVNCKVVSCSAG MACM_STRMA 112 7 -