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PDBsum entry 1mlz

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1mlz
Jmol
Contents
Protein chains
427 a.a. *
Ligands
TZA ×2
PLP ×2
Metals
_NA ×2
Waters ×324
* Residue conservation analysis
PDB id:
1mlz
Name: Transferase
Title: Crystal structure of 7,8-diaminopelargonic acid synthase in with the trans-isomer of amiclenomycin.
Structure: 7,8-diamino-pelargonic acid aminotransferase. Chain: a, b. Synonym: adenosylmethionine-8-amino-7-oxononanoate aminotra dapa aminotransferase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: bioa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.15Å     R-factor:   0.207     R-free:   0.240
Authors: J.Sandmark,S.Mann,A.Marquet,G.Schneider
Key ref:
J.Sandmark et al. (2002). Structural basis for the inhibition of the biosynthesis of biotin by the antibiotic amiclenomycin. J Biol Chem, 277, 43352-43358. PubMed id: 12218056 DOI: 10.1074/jbc.M207239200
Date:
02-Sep-02     Release date:   04-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P12995  (BIOA_ECOLI) -  Adenosylmethionine-8-amino-7-oxononanoate aminotransferase
Seq:
Struc:
429 a.a.
427 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.6.1.62  - Adenosylmethionine--8-amino-7-oxononanoate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + 8-amino-7-oxononanoate = S-adenosyl-4- methylthio-2-oxobutanoate + 7,8-diaminononanoate
S-adenosyl-L-methionine
+
8-amino-7-oxononanoate
Bound ligand (Het Group name = TZA)
matches with 80.00% similarity
= S-adenosyl-4- methylthio-2-oxobutanoate
+ 7,8-diaminononanoate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     biotin biosynthetic process   1 term 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M207239200 J Biol Chem 277:43352-43358 (2002)
PubMed id: 12218056  
 
 
Structural basis for the inhibition of the biosynthesis of biotin by the antibiotic amiclenomycin.
J.Sandmark, S.Mann, A.Marquet, G.Schneider.
 
  ABSTRACT  
 
The antibiotic amiclenomycin blocks the biosynthesis of biotin by inhibiting the pyridoxal-phosphate-dependent enzyme diaminopelargonic acid synthase. Inactivation of the enzyme is stereoselective, i.e. the cis isomer of amiclenomycin is a potent inhibitor, whereas the trans isomer is much less reactive. The crystal structure of the complex of the holoenzyme and amiclenomycin at 1.8 A resolution reveals that the internal aldimine linkage between the cofactor and the side chain of the catalytic residue Lys-274 is broken. Instead, a covalent bond is formed between the 4-amino nitrogen of amiclenomycin and the C4' carbon atom of pyridoxal-phosphate. The electron density for the bound inhibitor suggests that aromatization of the cyclohexadiene ring has occurred upon formation of the covalent adduct. This process could be initiated by proton abstraction at the C4 carbon atom of the cyclohexadiene ring, possibly by the proximal side chain of Lys-274, leading to the tautomer Schiff base followed by the removal of the second allylic hydrogen. The carboxyl tail of the amiclenomycin moiety forms a salt link to the conserved residue Arg-391 in the substrate-binding site. Modeling suggests steric hindrance at the active site as the determinant of the weak inhibiting potency of the trans isomer.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. Binding of amiclenomycin to DAPA synthase. A, stereo-view of cis ACM bound in the active site of DAPA synthase (subunit A). Hydrogen bonds (<3.2 Å distance between donor/acceptor atoms) are indicated by dashed lines. B, superposition of the two active sites in the DAPA synthase-PLP-cis ACM complex, illustrating the differences in the binding of the amiclenomycin moiety in the two subunits. Subunit A is shown in red and subunit B in blue.
Figure 6.
Fig. 6. Proposed mechanism of formation of the covalent aromatic adduct between amiclenomycin and PLP in the active site of DAPA synthase.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 43352-43358) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17898895 D.E.Scott, A.Ciulli, and C.Abell (2007).
Coenzyme biosynthesis: enzyme mechanism, structure and inhibition.
  Nat Prod Rep, 24, 1009-1026.  
16984394 S.Mann, and O.Ploux (2006).
7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies.
  FEBS J, 273, 4778-4789.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.