PDBsum entry 1auw

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Eye lens protein PDB id
Protein chains
447 a.a. *
Waters ×343
* Residue conservation analysis
PDB id:
Name: Eye lens protein
Title: H91n delta 2 crystallin from duck
Structure: Delta 2 crystallin. Chain: a, b, c, d. Engineered: yes. Mutation: yes
Source: Anas platyrhynchos. Organism_taxid: 8839. Cell_line: bl21. Organ: eye. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.50Å     R-factor:   0.161     R-free:   0.235
Authors: M.Abu-Abed,F.Vallee,P.L.Howell
Key ref:
M.Abu-Abed et al. (1997). Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91. Biochemistry, 36, 14012-14022. PubMed id: 9369472 DOI: 10.1021/bi971407s
03-Sep-97     Release date:   18-Mar-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P24058  (ARLY2_ANAPL) -  Argininosuccinate lyase
468 a.a.
447 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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

Urea Cycle and Arginine Biosynthesis
      Reaction: 2-(N(omega)-L-arginino)succinate = fumarate + L-arginine
= fumarate
+ L-arginine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cellular amino acid biosynthetic process   3 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1021/bi971407s Biochemistry 36:14012-14022 (1997)
PubMed id: 9369472  
Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91.
M.Abu-Abed, M.A.Turner, F.Vallée, A.Simpson, C.Slingsby, P.L.Howell.
The major soluble protein component of avian and reptilian eye lenses, delta crystallin, is highly homologous to the urea cycle enzyme, argininosuccinate lyase (ASL). In duck lenses there are two highly homologous delta crystallins, termed delta I and delta II, that are 94% identical in amino acid sequence. While delta II crystallin has been shown to exhibit ASL activity in vitro, delta I crystallin is inactive. The X-ray structure of a His to Asn mutant of duck delta II crystallin (H91N) has been determined to 2.5 A resolution using the molecular replacement technique. The overall fold of the protein is similar to other members of the superfamily to which this protein belongs, with the active site located in a cleft between three different monomers of the tetrameric protein. A reexamination of the kinetic properties of the H91N mutant reveals that the mutant has 10% wild-type activity. The Vmax of the mutant protein is identical to that of the wild-type protein, but a 10-fold increase in the Michaelis constant is seen, suggesting that His 91 is involved in binding the substrate. In an effort to determine the reasons for the loss of enzymatic activity in delta I crystallin, a structural comparison of the H91N mutant with the enzymatically inactive turkey delta I crystallin has been performed. This study revealed a remarkable similarity in the overall structures of the two proteins. Three regions of secondary structure do differ significantly between the two models; these include the N-terminal tail, a loop containing residues 76-91, and a cis versus trans peptide linkage at residue Thr 322. The cis to trans peptide variation appears to be an interspecies difference between turkey and duck and is therefore not directly involved in the loss of enzymatic activity. All the residues implicated in the catalytic mechanism are conserved in both the active and inactive proteins, and given the linearity of the relationship between the enzymatic activity of duck delta I/delta II heterotetramers and their delta II content (Piatigorsky & Horwitz, 1996), it is evident from the structure that only one of the three domains that contributes to the active site is responsible for the loss of activity in the delta I protein. Given the structural differences found in domain 1 (N-terminal tail and 76-91 loop), we postulate that these differences are responsible for the loss of catalytic activity in the delta I crystallin protein and that the delta I protein is inactive because it no longer binds the substrate.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20975998 K.Brown, M.X.Doss, S.Legros, J.Artus, A.K.Hadjantonakis, and A.C.Foley (2010).
eXtraembryonic ENdoderm (XEN) stem cells produce factors that activate heart formation.
  PLoS One, 5, e13446.  
  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.  
17326097 E.Trevisson, L.Salviati, M.C.Baldoin, I.Toldo, A.Casarin, S.Sacconi, L.Cesaro, G.Basso, and A.B.Burlina (2007).
Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene.
  Hum Mutat, 28, 694-702.  
17512708 M.J.Wagemaker, D.C.Eastwood, C.van der Drift, M.S.Jetten, K.Burton, L.J.Van Griensven, and H.J.Op den Camp (2007).
Argininosuccinate synthetase and argininosuccinate lyase: two ornithine cycle enzymes from Agaricus bisporus.
  Mycol Res, 111, 493-502.  
15273245 B.Yu, P.Paroutis, A.R.Davidson, and P.L.Howell (2004).
Disruption of a salt bridge dramatically accelerates subunit exchange in duck delta2 crystallin.
  J Biol Chem, 279, 40972-40979.  
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
14511381 H.J.Lee, S.W.Lu, and G.G.Chang (2003).
Monomeric molten globule intermediate involved in the equilibrium unfolding of tetrameric duck delta2-crystallin.
  Eur J Biochem, 270, 3988-3995.  
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
10866796 H.J.Lee, and G.G.Chang (2000).
Guanidine hydrochloride induced reversible dissociation and denaturation of duck delta2-crystallin.
  Eur J Biochem, 267, 3979-3985.  
  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.  
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.