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PDBsum entry 1f1o

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protein links
Lyase PDB id
1f1o
Jmol
Contents
Protein chain
351 a.a.* *
* Residue conservation analysis
* C-alpha coords only
PDB id:
1f1o
Name: Lyase
Title: Structural studies of adenylosuccinate lyases
Structure: Adenylosuccinate lyase. Chain: a. Synonym: asl. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.25Å     R-factor:   0.336     R-free:   0.355
Authors: E.A.Toth,T.Yeates
Key ref:
E.A.Toth et al. (2000). The crystal structure of adenylosuccinate lyase from Pyrobaculum aerophilum reveals an intracellular protein with three disulfide bonds. J Mol Biol, 301, 433-450. PubMed id: 10926519 DOI: 10.1006/jmbi.2000.3970
Date:
19-May-00     Release date:   10-Jan-01    
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12047  (PUR8_BACSU) -  Adenylosuccinate lyase
Seq:
Struc:
431 a.a.
351 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.4.3.2.2  - Adenylosuccinate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Purine Biosynthesis (late stages)
      Reaction:
1. N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP
2. (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamido)succinate = fumarate + 5-amino-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
N(6)-(1,2-dicarboxyethyl)AMP
= fumarate
+ AMP
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamido)succinate
= fumarate
+ 5-amino-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     'de novo' AMP biosynthetic process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2000.3970 J Mol Biol 301:433-450 (2000)
PubMed id: 10926519  
 
 
The crystal structure of adenylosuccinate lyase from Pyrobaculum aerophilum reveals an intracellular protein with three disulfide bonds.
E.A.Toth, C.Worby, J.E.Dixon, E.R.Goedken, S.Marqusee, T.O.Yeates.
 
  ABSTRACT  
 
Adenylosuccinate lyase catalyzes two separate reactions in the de novo purine biosynthetic pathway. Through its dual action in this pathway, adenylosuccinate lyase plays an integral part in cellular replication and metabolism. Mutations in the human enzyme can result in severe neurological disorders, including mental retardation with autistic features. The crystal structure of adenylosuccinate lyase from the hyperthermophilic archaebacterium Pyrobaculum aerophilum has been determined to 2.1 A resolution. Although both the fold of the monomer and the architecture of the tetrameric assembly are similar to adenylosuccinate lyase from the thermophilic eubacterium Thermotoga maritima, the archaebacterial lyase contains unique features. Surprisingly, the structure of adenylosuccinate lyase from P. aerophilum reveals that this intracellular protein contains three disulfide bonds that contribute significantly to its stability against thermal and chemical denaturation. The observation of multiple disulfide bonds in the recombinant form of the enzyme suggests the need for further investigations into whether the intracellular environment of P. aerophilum, and possibly other hyperthermophiles, may be compatible with protein disulfide bond formation. In addition, the protein is shorter in P. aerophilum than it is in other organisms. This abbreviation results from an internal excision of a cluster of helices that may be involved in protein-protein interactions in other organisms and may relate to the observed clinical effects of human mutations in that region.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Disulfide bonds in P. aerophilum ASL. (a) The Cys37-Cys50 and Cys49-Cys87 disulfide bonds of domain 1. (b) The Cys167-Cys403 disulfide bond that tethers the C-terminal extension to domain 2. Domain 2 is blue, and the C-terminal extension is red.
Figure 6.
Figure 6. Stereo view of the superimposed active sites of P. aerophilum ASL and T. maritima ASL. The active-site residues of P. aerophilum ASL are red and the active-site residues of T. maritima ASL are black.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 301, 433-450) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20857210 T.Yuan, J.R.Gu, W.B.Gu, J.Wu, S.R.Ge, and H.Xu (2011).
Molecular cloning, characterization and expression analysis of adenylosuccinate lyase gene in grass carp (Ctenopharyngodon idella).
  Mol Biol Rep, 38, 2059-2065.  
20483913 A.Guelorget, M.Roovers, V.Guérineau, C.Barbey, X.Li, and B.Golinelli-Pimpaneau (2010).
Insights into the hyperthermostability and unusual region-specificity of archaeal Pyrococcus abyssi tRNA m1A57/58 methyltransferase.
  Nucleic Acids Res, 38, 6206-6218.
PDB codes: 3lga 3lhd 3mb5
20693687 P.K.Fyfe, A.Dawson, M.T.Hutchison, S.Cameron, and W.N.Hunter (2010).
Structure of Staphylococcus aureus adenylosuccinate lyase (PurB) and assessment of its potential as a target for structure-based inhibitor discovery.
  Acta Crystallogr D Biol Crystallogr, 66, 881-888.
PDB code: 2x75
19740110 G.Cacciapuoti, I.Peluso, F.Fuccio, and M.Porcelli (2009).
Purine nucleoside phosphorylases from hyperthermophilic Archaea require a CXC motif for stability and folding.
  FEBS J, 276, 5799-5805.  
18513746 N.P.King, T.M.Lee, M.R.Sawaya, D.Cascio, and T.O.Yeates (2008).
Structures and functional implications of an AMP-binding cystathionine beta-synthase domain protein from a hyperthermophilic archaeon.
  J Mol Biol, 380, 181-192.
PDB codes: 2rif 2rih
17508126 R.Ladenstein, and B.Ren (2008).
Reconsideration of an early dogma, saying "there is no evidence for disulfide bonds in proteins from archaea".
  Extremophiles, 12, 29-38.  
19111067 R.R.Thangudu, M.Manoharan, N.Srinivasan, F.Cadet, R.Sowdhamini, and B.Offmann (2008).
Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families.
  BMC Struct Biol, 8, 55.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17395198 D.R.Boutz, D.Cascio, J.Whitelegge, L.J.Perry, and T.O.Yeates (2007).
Discovery of a thermophilic protein complex stabilized by topologically interlinked chains.
  J Mol Biol, 368, 1332-1344.
PDB code: 2ibp
17419725 G.Cacciapuoti, S.Gorassini, M.F.Mazzeo, R.A.Siciliano, V.Carbone, V.Zappia, and M.Porcelli (2007).
Biochemical and structural characterization of mammalian-like purine nucleoside phosphorylase from the Archaeon Pyrococcus furiosus.
  FEBS J, 274, 2482-2495.  
17635906 L.D.Cabrita, J.A.Irving, M.C.Pearce, J.C.Whisstock, and S.P.Bottomley (2007).
Aeropin from the extremophile Pyrobaculum aerophilum bypasses the serpin misfolding trap.
  J Biol Chem, 282, 26802-26809.  
18073113 M.Kuratani, Y.Yoshikawa, Y.Bessho, K.Higashijima, T.Ishii, R.Shibata, S.Takahashi, K.Yutani, and S.Yokoyama (2007).
Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine.
  Structure, 15, 1642-1653.
PDB codes: 2e21 2e89
16930136 R.Ladenstein, and B.Ren (2006).
Protein disulfides and protein disulfide oxidoreductases in hyperthermophiles.
  FEBS J, 273, 4170-4185.  
  16403972 C.Crifò, W.Siems, S.Soro, and C.Salerno (2005).
Inhibition of defective adenylosuccinate lyase by HNE: a neurological disease that may be affected by oxidative stress.
  Biofactors, 24, 131-136.  
15819883 G.Cacciapuoti, S.Forte, M.A.Moretti, A.Brio, V.Zappia, and M.Porcelli (2005).
A novel hyperthermostable 5'-deoxy-5'-methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus.
  FEBS J, 272, 1886-1899.  
16148304 J.Eichler, and M.W.Adams (2005).
Posttranslational protein modification in Archaea.
  Microbiol Mol Biol Rev, 69, 393-425.  
16111437 M.Beeby, B.D.O'Connor, C.Ryttersgaard, D.R.Boutz, L.J.Perry, and T.O.Yeates (2005).
The genomics of disulfide bonding and protein stabilization in thermophiles.
  PLoS Biol, 3, e309.
PDB code: 1rki
15606771 G.Cacciapuoti, M.A.Moretti, S.Forte, A.Brio, L.Camardella, V.Zappia, and M.Porcelli (2004).
Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus. Mechanism of the reaction and assignment of disulfide bonds.
  Eur J Biochem, 271, 4834-4844.  
14739239 M.Roovers, J.Wouters, J.M.Bujnicki, C.Tricot, V.Stalon, H.Grosjean, and L.Droogmans (2004).
A primordial RNA modification enzyme: the case of tRNA (m1A) methyltransferase.
  Nucleic Acids Res, 32, 465-476.  
15130478 Y.Xu, R.Zhang, A.Joachimiak, P.D.Carr, T.Huber, S.G.Vasudevan, and D.L.Ollis (2004).
Structure of the N-terminal domain of Escherichia coli glutamine synthetase adenylyltransferase.
  Structure, 12, 861-869.
PDB code: 1v4a
13678528 R.Ortenberg, and J.Beckwith (2003).
Functions of thiol-disulfide oxidoreductases in E. coli: redox myths, realities, and practicalities.
  Antioxid Redox Signal, 5, 403-411.  
12107280 P.Mallick, D.R.Boutz, D.Eisenberg, and T.O.Yeates (2002).
Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds.
  Proc Natl Acad Sci U S A, 99, 9679-9684.  
11722571 J.R.Cort, S.V.Mariappan, C.Y.Kim, M.S.Park, T.S.Peat, G.S.Waldo, T.C.Terwilliger, and M.A.Kennedy (2001).
Solution structure of Pyrobaculum aerophilum DsrC, an archaeal homologue of the gamma subunit of dissimilatory sulfite reductase.
  Eur J Biochem, 268, 5842-5850.
PDB code: 1ji8
11489901 T.C.Appleby, I.I.Mathews, M.Porcelli, G.Cacciapuoti, and S.E.Ealick (2001).
Three-dimensional structure of a hyperthermophilic 5'-deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus.
  J Biol Chem, 276, 39232-39242.
PDB codes: 1jds 1jdt 1jdu 1jdv 1jdz 1je0 1je1 1jp7 1jpv
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 codes are shown on the right.