spacer
spacer

PDBsum entry 1bs0

Go to PDB code: 
protein ligands links
Transferase PDB id
1bs0
Jmol
Contents
Protein chain
383 a.a. *
Ligands
SO4 ×3
Waters ×581
* Residue conservation analysis
PDB id:
1bs0
Name: Transferase
Title: Plp-dependent acyl-coa synthase
Structure: Protein (8-amino-7-oxonanoate synthase). Chain: a. Synonym: aons, 8-amino-7-ketopelargonate synthase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Strain: b834(de3). Gene: biof. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.65Å     R-factor:   0.178     R-free:   0.212
Authors: D.Alexeev,M.Alexeeva,R.L.Baxter,D.J.Campopiano,S.P.Webster,L
Key ref:
D.Alexeev et al. (1998). The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J Mol Biol, 284, 401-419. PubMed id: 9813126 DOI: 10.1006/jmbi.1998.2086
Date:
31-Aug-98     Release date:   27-Aug-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12998  (BIOF_ECOLI) -  8-amino-7-oxononanoate synthase
Seq:
Struc:
384 a.a.
383 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.47  - 8-amino-7-oxononanoate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Pimeloyl-[acyl-carrier protein] + L-alanine = 8-amino-7-oxononanoate + CO2 + holo-[acyl-carrier protein]
Pimeloyl-[acyl-carrier protein]
+ L-alanine
= 8-amino-7-oxononanoate
+ CO(2)
+ holo-[acyl-carrier protein]
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1998.2086 J Mol Biol 284:401-419 (1998)
PubMed id: 9813126  
 
 
The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme.
D.Alexeev, M.Alexeeva, R.L.Baxter, D.J.Campopiano, S.P.Webster, L.Sawyer.
 
  ABSTRACT  
 
8-Amino-7-oxononanoate synthase (or 8-amino-7-ketopelargonate synthase; EC 2.3.1.47; AONS) catalyses the decarboxylative condensation of l-alanine and pimeloyl-CoA in the first committed step of biotin biosynthesis. We have cloned, over-expressed and purified AONS from Escherichia coli and determined the crystal structures of the apo and PLP-bound forms of the enzyme. The protein is a symmetrical homodimer with a tertiary structure and active site organisation similar to, but distinct from, those of other PLP-dependent enzymes whose three-dimensional structures are known. The critical PLP-binding lysine of AONS is located at the end of a deep cleft that allows access of the pantothenate arm of pimeloyl-CoA. A cluster of positively charged residues at the entrance to this cleft forms a putative diphosphate binding site for CoA. The structure of E. coli AONS enables identification of the key residues of the PLP-binding site and thus provides a framework with which to understand the biochemical mechanism, which is similar to that catalysed by 5-aminolevulinate synthase and two other alpha-oxoamine synthases. Although AONS has a low overall sequence similarity with the catalytic domains of other alpha-oxoamine synthases, the structure reveals the regions of significant identity to be functionally important. This suggests that the organisation of the conserved catalytic residues in the active site is similar for all enzymes of this sub-class of PLP-dependent enzymes and they share a common mechanism. Knowledge of the three-dimensional structure of AONS will enable characterisation of the structural features of this enzyme sub-family that are responsible for this important type of reaction.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. (a) Reactions catalysed by the acyl-CoA transferases. For 8-amino-7-oxononanoate synthase (AONS; E.C. 2.3.1.47), R = CH3 and R = (CH2)4CO-2 ; for 5-aminolevulinate synthase (ALAS, E.C. 2.3.1.37), R = H and R0 = CH2CO-2 ; for serine palmitoyltransferase (SPT, E.C. 2.3.1.50), R = CH2OH and R0 = (CH2)14CH3; and for 2-amino- 3-oxobutyrate CoA ligase (AKB, E.C. 2.3.1.29), R = R0 = H. (b) Proposed mechanism for AONS where R = CH3, R0 = (CH2)4CO-2 and P = OPO3 2- .
Figure 8.
Figure 8. Stereo drawings of the empty active site for the AONS apo-enzyme structure (top) and of the PLP-bound form (bottom). The domain colours are as in Figures 4, 5 and 6. Most of the active-site residues belong to the major domain (purple), Asn47 and Tyr49 come from the N-terminal domain (blue), Arg361 comes from the C-terminal domain (yellow), Tyr264 and Thr266 belong to the major domain (grey) that comes from the symmetry-related mono- mer of the dimer. Important side-chains are shown as balls and sticks.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 284, 401-419) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20445930 J.Lowther, B.A.Yard, K.A.Johnson, L.G.Carter, V.T.Bhat, M.C.Raman, D.J.Clarke, B.Ramakers, S.A.McMahon, J.H.Naismith, and D.J.Campopiano (2010).
Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation.
  Mol Biosyst, 6, 1682-1693.
PDB code: 2xbn
20370823 K.Nishio, K.Ogasahara, Y.Morimoto, T.Tsukihara, S.J.Lee, and K.Yutani (2010).
Large conformational changes in the Escherichia coli tryptophan synthase beta(2) subunit upon pyridoxal 5'-phosphate binding.
  FEBS J, 277, 2157-2170.
PDB codes: 2dh5 2dh6
20578000 M.C.Raman, K.A.Johnson, D.J.Clarke, J.H.Naismith, and D.J.Campopiano (2010).
The serine palmitoyltransferase from Sphingomonas wittichii RW1: An interesting link to an unusual acyl carrier protein.
  Biopolymers, 93, 811-822.
PDB code: 2x8u
19416851 G.Han, S.D.Gupta, K.Gable, S.Niranjanakumari, P.Moitra, F.Eichler, R.H.Brown, J.M.Harmon, and T.M.Dunn (2009).
Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities.
  Proc Natl Acad Sci U S A, 106, 8186-8191.  
19376777 M.C.Raman, K.A.Johnson, B.A.Yard, J.Lowther, L.G.Carter, J.H.Naismith, and D.J.Campopiano (2009).
The External Aldimine Form of Serine Palmitoyltransferase: STRUCTURAL, KINETIC, AND SPECTROSCOPIC ANALYSIS OF THE WILD-TYPE ENZYME AND HSAN1 MUTANT MIMICS.
  J Biol Chem, 284, 17328-17339.
PDB codes: 2w8j 2w8t 2w8u 2w8v 2w8w
19838203 R.C.Kelly, M.E.Bolitho, D.A.Higgins, W.Lu, W.L.Ng, P.D.Jeffrey, J.D.Rabinowitz, M.F.Semmelhack, F.M.Hughson, and B.L.Bassler (2009).
The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA.
  Nat Chem Biol, 5, 891-895.
PDB codes: 3hqt 3kki
19562746 T.Lendrihas, J.Zhang, G.A.Hunter, and G.C.Ferreira (2009).
Arg-85 and Thr-430 in murine 5-aminolevulinate synthase coordinate acyl-CoA-binding and contribute to substrate specificity.
  Protein Sci, 18, 1847-1859.  
19346561 Y.Shiraiwa, H.Ikushiro, and H.Hayashi (2009).
Multifunctional role of his159in the catalytic reaction of serine palmitoyltransferase.
  J Biol Chem, 284, 15487-15495.  
18411263 T.Spirig, A.Tiaden, P.Kiefer, C.Buchrieser, J.A.Vorholt, and H.Hilbi (2008).
The Legionella autoinducer synthase LqsA produces an alpha-hydroxyketone signaling molecule.
  J Biol Chem, 283, 18113-18123.  
17485466 G.A.Hunter, J.Zhang, and G.C.Ferreira (2007).
Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase.
  J Biol Chem, 282, 23025-23035.  
17557831 H.Ikushiro, M.M.Islam, H.Tojo, and H.Hayashi (2007).
Molecular characterization of membrane-associated soluble serine palmitoyltransferases from Sphingobacterium multivorum and Bdellovibrio stolpii.
  J Bacteriol, 189, 5749-5761.  
17469798 T.D.Turbeville, J.Zhang, G.A.Hunter, and G.C.Ferreira (2007).
Histidine 282 in 5-aminolevulinate synthase affects substrate binding and catalysis.
  Biochemistry, 46, 5972-5981.  
18071260 T.Kubota, J.Shimono, C.Kanameda, and Y.Izumi (2007).
The first thermophilic alpha-oxoamine synthase family enzyme that has activities of 2-amino-3-ketobutyrate CoA ligase and 7-keto-8-aminopelargonic acid synthase: cloning and overexpression of the gene from an extreme thermophile, Thermus thermophilus, and characterization of its gene product.
  Biosci Biotechnol Biochem, 71, 3033-3040.  
16557306 D.Alexeev, R.L.Baxter, D.J.Campopiano, O.Kerbarh, L.Sawyer, N.Tomczyk, R.Watt, and S.P.Webster (2006).
Suicide inhibition of alpha-oxamine synthases: structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine.
  Org Biomol Chem, 4, 1209-1212.
PDB code: 2g6w
16935983 M.J.Percy, R.J.Cuthbert, A.May, and M.F.McMullin (2006).
A novel mutation, Ile289Thr, in the ALAS2 gene in a family with pyridoxine responsive sideroblastic anaemia.
  J Clin Pathol, 59, 1002.  
16353092 O.Kerbarh, D.J.Campopiano, and R.L.Baxter (2006).
Mechanism of alpha-oxoamine synthases: identification of the intermediate Claisen product in the 8-amino-7-oxononanoate synthase reaction.
  Chem Commun (Camb), (), 60-62.  
17146529 Q.Bashir, N.Rashid, and M.Akhtar (2006).
Mechanism and substrate stereochemistry of 2-amino-3-oxobutyrate CoA ligase: implications for 5-aminolevulinate synthase and related enzymes.
  Chem Commun (Camb), (), 5065-5067.  
16769720 V.M.Bhor, S.Dev, G.R.Vasanthakumar, P.Kumar, S.Sinha, and A.Surolia (2006).
Broad substrate stereospecificity of the Mycobacterium tuberculosis 7-keto-8-aminopelargonic acid synthase: Spectroscopic and kinetic studies.
  J Biol Chem, 281, 25076-25088.  
16121195 I.Astner, J.O.Schulze, J.van den Heuvel, D.Jahn, W.D.Schubert, and D.W.Heinz (2005).
Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans.
  EMBO J, 24, 3166-3177.
PDB codes: 2bwn 2bwo 2bwp
15840827 J.Zhang, A.V.Cheltsov, and G.C.Ferreira (2005).
Conversion of 5-aminolevulinate synthase into a more active enzyme by linking the two subunits: spectroscopic and kinetic properties.
  Protein Sci, 14, 1190-1200.  
15791207 T.Nakai, N.Nakagawa, N.Maoka, R.Masui, S.Kuramitsu, and N.Kamiya (2005).
Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia.
  EMBO J, 24, 1523-1536.
PDB codes: 1wyt 1wyu 1wyv
15498941 A.Paiardini, F.Bossa, and S.Pascarella (2004).
Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
  Protein Sci, 13, 2992-3005.  
15485854 G.Han, K.Gable, L.Yan, M.Natarajan, J.Krishnamurthy, S.D.Gupta, A.Borovitskaya, J.M.Harmon, and T.M.Dunn (2004).
The topology of the Lcb1p subunit of yeast serine palmitoyltransferase.
  J Biol Chem, 279, 53707-53716.  
12736261 A.V.Cheltsov, W.C.Guida, and G.C.Ferreira (2003).
Circular permutation of 5-aminolevulinate synthase: effect on folding, conformational stability, and structure.
  J Biol Chem, 278, 27945-27955.  
12464627 S.Yasuda, M.Nishijima, and K.Hanada (2003).
Localization, topology, and function of the LCB1 subunit of serine palmitoyltransferase in mammalian cells.
  J Biol Chem, 278, 4176-4183.  
12185836 E.Monaghan, K.Gable, and T.Dunn (2002).
Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the requirement for the TSC3 gene in Saccharomyces cerevisiae.
  Yeast, 19, 659-670.  
12191993 J.Zhang, and G.C.Ferreira (2002).
Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism.
  J Biol Chem, 277, 44660-44669.  
  12417569 K.Bejaoui, Y.Uchida, S.Yasuda, M.Ho, M.Nishijima, R.H.Brown, W.M.Holleran, and K.Hanada (2002).
Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis.
  J Clin Invest, 110, 1301-1308.  
11781309 K.Gable, G.Han, E.Monaghan, D.Bacikova, M.Natarajan, R.Williams, and T.M.Dunn (2002).
Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase.
  J Biol Chem, 277, 10194-10200.  
11737206 R.Contestabile, A.Paiardini, S.Pascarella, M.L.di Salvo, S.D'Aguanno, and F.Bossa (2001).
l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions.
  Eur J Biochem, 268, 6508-6525.  
10712613 A.J.Edgar, and J.M.Polak (2000).
Molecular cloning of the human and murine 2-amino-3-ketobutyrate coenzyme A ligase cDNAs.
  Eur J Biochem, 267, 1805-1812.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10880431 H.I.Krupka, R.Huber, S.C.Holt, and T.Clausen (2000).
Crystal structure of cystalysin from Treponema denticola: a pyridoxal 5'-phosphate-dependent protein acting as a haemolytic enzyme.
  EMBO J, 19, 3168-3178.
PDB codes: 1c7n 1c7o
10713067 K.Gable, H.Slife, D.Bacikova, E.Monaghan, and T.M.Dunn (2000).
Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity.
  J Biol Chem, 275, 7597-7603.  
11106504 L.Feng, M.K.Geck, A.C.Eliot, and J.F.Kirsch (2000).
Aminotransferase activity and bioinformatic analysis of 1-aminocyclopropane-1-carboxylate synthase.
  Biochemistry, 39, 15242-15249.  
10788513 L.McIver, R.L.Baxter, and D.J.Campopiano (2000).
Identification of the [Fe-S] cluster-binding residues of Escherichia coli biotin synthase.
  J Biol Chem, 275, 13888-13894.  
10691982 R.Talwar, J.R.Jagath, N.A.Rao, and H.S.Savithri (2000).
His230 of serine hydroxymethyltransferase facilitates the proton abstraction step in catalysis.
  Eur J Biochem, 267, 1441-1446.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.