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PDBsum entry 1aos

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protein Protein-protein interface(s) links
Lyase PDB id
1aos
Jmol
Contents
Protein chain
434 a.a. *
* Residue conservation analysis
PDB id:
1aos
Name: Lyase
Title: Human argininosuccinate lyase
Structure: Argininosuccinate lyase. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Cellular_location: cytoplasm. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
4.20Å     R-factor:   0.188     R-free:   0.298
Authors: M.A.Turner,A.Simpson,R.R.Mcinnes,P.L.Howell
Key ref:
M.A.Turner et al. (1997). Human argininosuccinate lyase: a structural basis for intragenic complementation. Proc Natl Acad Sci U S A, 94, 9063-9068. PubMed id: 9256435 DOI: 10.1073/pnas.94.17.9063
Date:
10-Jul-97     Release date:   14-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04424  (ARLY_HUMAN) -  Argininosuccinate lyase
Seq:
Struc:
464 a.a.
434 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.4.3.2.1  - Argininosuccinate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Urea Cycle and Arginine Biosynthesis
      Reaction: 2-(N(omega)-L-arginino)succinate = fumarate + L-arginine
2-(N(omega)-L-arginino)succinate
= fumarate
+ L-arginine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     small molecule metabolic process   8 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.94.17.9063 Proc Natl Acad Sci U S A 94:9063-9068 (1997)
PubMed id: 9256435  
 
 
Human argininosuccinate lyase: a structural basis for intragenic complementation.
M.A.Turner, A.Simpson, R.R.McInnes, P.L.Howell.
 
  ABSTRACT  
 
Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R). To understand the structural basis of the Q286R:D87G intragenic complementation event at the ASL locus, we have determined the x-ray crystal structure of recombinant human ASL at 4. 0 A resolution. The structure has been refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2-fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of space group P3121 completes the tetramer. Each of the four active sites is composed of residues from three monomers. Structural mapping of the Q286R and D87G mutations indicate that both are near the active site and each is contributed by a different monomer. Thus when mutant monomers combine randomly such that one active site contains both mutations, it is required by molecular symmetry that another active site exists with no mutations. These "native" active sites give rise to the observed partial recovery of enzymatic activity.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. The three regions of high sequence conservation among members of the ASL superfamily. ASL, argininosuccinate lyase; D2C, II crystallin; fumarase, E. coli fumarase C; aspartase, E. coli aspartase; CMLE, P. putida 3-carboxy-cis,cis-muconate lactonizing enzyme; ADS, B. subtilis adenylosuccinase.
Figure 4.
Fig. 4. Schematic diagrams showing the arrangement of the conserved regions (shaded in black) in (a) the tetramer and (b) the active^ site. The location of key residues are shown in a ball-and-stick representation. The residues are labeled according to the monomer on which they reside (A-D) and the residue number and type.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21312326 A.Erez, S.C.Nagamani, and B.Lee (2011).
Argininosuccinate lyase deficiency-Argininosuccinic aciduria and beyond.
  Am J Med Genet C Semin Med Genet, 157, 45-53.  
20298553 F.Imtiaz, M.Al-Sayed, D.Trabzuni, B.R.Al-Mubarak, O.Alsmadi, M.S.Rashed, and B.F.Meyer (2010).
Novel mutations underlying argininosuccinic aciduria in Saudi Arabia.
  BMC Res Notes, 3, 79.  
19674108 C.W.Huang, C.C.Tseng, Y.H.Chen, Y.H.Chen, W.Y.Chou, and H.J.Lee (2009).
Substitution of residues at the double dimer interface affects the stability and oligomerization of goose delta-crystallin.
  FEBS J, 276, 5126-5136.  
  19936305 C.W.Huang, Y.H.Chen, Y.H.Chen, Y.C.Tsai, and H.J.Lee (2009).
The interaction of Glu294 at the subunit interface is important for the activity and stability of goose delta-crystallin.
  Mol Vis, 15, 2358-2363.  
19703900 E.Trevisson, A.Burlina, M.Doimo, V.Pertegato, A.Casarin, L.Cesaro, P.Navas, G.Basso, G.Sartori, and L.Salviati (2009).
Functional complementation in yeast allows molecular characterization of missense argininosuccinate lyase mutations.
  J Biol Chem, 284, 28926-28934.  
  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
17513375 F.Y.Yin, Y.H.Chen, C.M.Yu, Y.C.Pon, and H.J.Lee (2007).
Kinetic refolding barrier of guanidinium chloride denatured goose delta-crystallin leads to regular aggregate formation.
  Biophys J, 93, 1235-1245.  
16597988 B.Bäuerle, Z.Cokesa, S.Hofmann, and P.G.Rieger (2006).
Sequencing and heterologous expression of an epimerase and two lyases from iminodisuccinate-degrading bacteria.
  Appl Environ Microbiol, 72, 2824-2828.  
15662599 H.U.Bender, S.Almashanu, G.Steel, C.A.Hu, W.W.Lin, A.Willis, A.Pulver, and D.Valle (2005).
Functional consequences of PRODH missense mutations.
  Am J Hum Genet, 76, 409-420.  
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
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.  
11258884 L.M.Sampaleanu, F.Vallée, C.Slingsby, and P.L.Howell (2001).
Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis.
  Biochemistry, 40, 2732-2742.
PDB codes: 1hy0 1hy1 1i0a
10673438 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.
PDB codes: 1c3c 1c3u
11063569 J.L.Brosius, and R.F.Colman (2000).
A key role in catalysis for His89 of adenylosuccinate lyase of Bacillus subtilis.
  Biochemistry, 39, 13336-13343.  
10029537 A.R.Chakraborty, A.Davidson, and P.L.Howell (1999).
Mutational analysis of amino acid residues involved in argininosuccinate lyase activity in duck delta II crystallin.
  Biochemistry, 38, 2435-2443.  
10029536 F.Vallée, M.A.Turner, P.L.Lindley, and P.L.Howell (1999).
Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate.
  Biochemistry, 38, 2425-2434.
PDB code: 1dcn
  10091655 L.M.Sampaleanu, A.R.Davidson, C.Graham, G.J.Wistow, and P.L.Howell (1999).
Domain exchange experiments in duck delta-crystallins: functional and evolutionary implications.
  Protein Sci, 8, 529-537.  
10220900 R.Cohen-Kupiec, M.Kupiec, K.Sandbeck, and J.A.Leigh (1999).
Functional conservation between the argininosuccinate lyase of the archaeon Methanococcus maripaludis and the corresponding bacterial and eukaryal genes.
  FEMS Microbiol Lett, 173, 231-238.  
10220322 T.F.Schwede, J.Rétey, and G.E.Schulz (1999).
Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile.
  Biochemistry, 38, 5355-5361.
PDB code: 1b8f
9890879 T.T.Lee, C.Worby, Z.Q.Bao, J.E.Dixon, and R.F.Colman (1999).
His68 and His141 are critical contributors to the intersubunit catalytic site of adenylosuccinate lyase of Bacillus subtilis.
  Biochemistry, 38, 22-32.  
9369472 M.Abu-Abed, M.A.Turner, F.Vallée, A.Simpson, C.Slingsby, and P.L.Howell (1997).
Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91.
  Biochemistry, 36, 14012-14022.
PDB code: 1auw
9335052 O.Zoubenko, F.Uckun, Y.Hur, I.Chet, and N.Tumer (1997).
Plant resistance to fungal infection induced by nontoxic pokeweed antiviral protein mutants.
  Nat Biotechnol, 15, 992-996.  
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.