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PDBsum entry 1c3u

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1c3u
Jmol
Contents
Protein chains
423 a.a. *
Ligands
SO4 ×4
Waters ×392
* Residue conservation analysis
PDB id:
1c3u
Name: Lyase
Title: T. Maritima adenylosuccinate lyase
Structure: Adenylosuccinate lyase. Chain: a, b. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.30Å     R-factor:   0.199     R-free:   0.230
Authors: E.A.Toth,T.O.Yeates
Key ref:
E.A.Toth and T.O.Yeates (2000). The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway. Structure, 8, 163-174. PubMed id: 10673438 DOI: 10.1016/S0969-2126(00)00092-7
Date:
28-Jul-99     Release date:   08-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9X0I0  (PUR8_THEMA) -  Adenylosuccinate lyase
Seq:
Struc:
431 a.a.
423 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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   4 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(00)00092-7 Structure 8:163-174 (2000)
PubMed id: 10673438  
 
 
The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway.
E.A.Toth, T.O.Yeates.
 
  ABSTRACT  
 
Background: Adenylosuccinate lyase is an enzyme that plays a critical role in both cellular replication and metabolism via its action in the de novo purine biosynthetic pathway. Adenylosuccinate lyase is the only enzyme in this pathway to catalyze two separate reactions, enabling it to participate in the addition of a nitrogen at two different positions in adenosine monophosphate. Both reactions catalyzed by adenylosuccinate lyase involve the beta-elimination of fumarate. Enzymes that catalyze this type of reaction belong to a superfamily, the members of which are homotetramers. Because adenylosuccinate lyase plays an integral part in maintaining proper cellular metabolism, mutations in the human enzyme can have severe clinical consequences, including mental retardation with autistic features. Results: The 1.8 A crystal structure of adenylosuccinate lyase from Thermotoga maritima has been determined by multiwavelength anomalous dispersion using the selenomethionine-substituted enzyme. The fold of the monomer is reminiscent of other members of the beta-elimination superfamily. However, its active tetrameric form exhibits striking differences in active-site architecture and cleft size. Conclusions: This first structure of an adenylosuccinate lyase reveals that, along with the catalytic base (His141) and the catalytic acid (His68), Gln212 and Asn270 might play a vital role in catalysis by properly orienting the succinyl moiety of the substrates. We propose a model for the dual activity of adenylosuccinate lyase: a single 180 degrees bond rotation must occur in the substrate between the first and second enzymatic reactions. Modeling of the pathogenic human S413P mutation indicates that the mutation destabilizes the enzyme by disrupting the C-terminal extension.
 
  Selected figure(s)  
 
Figure 8.
Figure 8. Mapping of the S413P human ASL mutation to the T. maritima ASL structure. The residue singled out by directional profiles (Asp406) is colored green. The residue singled out by the extensible threading calculator (ETC) method (Thr404) is colored cyan. The C-terminal extension is colored red. This figure was generated using RIBBONS [36].
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 163-174) copyright 2000.  
  Figure was 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.  
20549362 G.Allegri, M.J.Fernandes, F.B.Scalco, P.Correia, R.E.Simoni, J.C.Llerena, and M.L.de Oliveira (2010).
Fumaric aciduria: an overview and the first Brazilian case report.
  J Inherit Metab Dis, 33, 411-419.  
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
  19724117 G.Kozlov, L.Nguyen, J.Pearsall, and K.Gehring (2009).
The structure of phosphate-bound Escherichia coli adenylosuccinate lyase identifies His171 as a catalytic acid.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 857-861.
PDB code: 3gzh
18469177 S.Sivendran, and R.F.Colman (2008).
Effect of a new non-cleavable substrate analog on wild-type and serine mutants in the signature sequence of adenylosuccinate lyase of Bacillus subtilis and Homo sapiens.
  Protein Sci, 17, 1162-1174.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17322529 M.L.Segall, M.A.Cashman, and R.F.Colman (2007).
Important roles of hydroxylic amino acid residues in the function of Bacillus subtilis adenylosuccinate lyase.
  Protein Sci, 16, 441-448.  
17600142 S.Sivendran, M.L.Segall, P.C.Rancy, and R.F.Colman (2007).
Effect of Asp69 and Arg310 on the pK of His68, a key catalytic residue of adenylosuccinate lyase.
  Protein Sci, 16, 1700-1707.  
  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.  
15502303 P.Bhaumik, M.K.Koski, U.Bergmann, and R.K.Wierenga (2004).
Structure determination and refinement at 2.44 A resolution of argininosuccinate lyase from Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 60, 1964-1970.
PDB code: 1tj7
15471876 S.Sivendran, D.Patterson, E.Spiegel, I.McGown, D.Cowley, and R.F.Colman (2004).
Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL.
  J Biol Chem, 279, 53789-53797.  
12876319 J.B.Palenchar, J.M.Crocco, and R.F.Colman (2003).
The characterization of mutant Bacillus subtilis adenylosuccinate lyases corresponding to severe human adenylosuccinate lyase deficiencies.
  Protein Sci, 12, 1694-1705.  
11841213 J.L.Brosius, and R.F.Colman (2002).
Three subunits contribute amino acids to the active site of tetrameric adenylosuccinate lyase: Lys268 and Glu275 are required.
  Biochemistry, 41, 2217-2226.  
11698398 L.M.Sampaleanu, B.Yu, and P.L.Howell (2002).
Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase.
  J Biol Chem, 277, 4166-4175.
PDB code: 1k7w
11006546 T.J.Kappock, S.E.Ealick, and J.Stubbe (2000).
Modular evolution of the purine biosynthetic pathway.
  Curr Opin Chem Biol, 4, 567-572.  
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.