PDBsum entry 3lxc

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Hydrolase PDB id
Protein chain
391 a.a. *
NAG ×2
GOL ×2
Waters ×552
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Interconversion of human lysosomal enzyme specificities
Structure: Alpha-galactosidase a. Chain: a, b. Fragment: unp residues 32-429. Synonym: alpha-d-galactoside galactohydrolase, alpha-d-gala a, melibiase. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gla. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
2.35Å     R-factor:   0.186     R-free:   0.237
Authors: I.B.Tomasic,M.C.Metcalf,A.I.Guce,N.E.Clark,S.C.Garman
Key ref: I.B.Tomasic et al. (2010). Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases. J Biol Chem, 285, 21560-21566. PubMed id: 20444686
25-Feb-10     Release date:   05-May-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06280  (AGAL_HUMAN) -  Alpha-galactosidase A
429 a.a.
391 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Alpha-galactosidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Melibiose + H2O = galactose + glucose

      Cofactor: Mg(2+); NAD(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   6 terms 
  Biological process     metabolic process   11 terms 
  Biochemical function     catalytic activity     10 terms  


J Biol Chem 285:21560-21566 (2010)
PubMed id: 20444686  
Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases.
I.B.Tomasic, M.C.Metcalf, A.I.Guce, N.E.Clark, S.C.Garman.
The human lysosomal enzymes alpha-galactosidase (alpha-GAL, EC and alpha-N-acetylgalactosaminidase (alpha-NAGAL, EC share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of alpha- GAL and alpha-NAGAL. The engineered alpha-GAL (which we call alpha-GAL(SA)) retains the antigenicity of alpha-GAL but has acquired the enzymatic specificity of alpha-NAGAL. Conversely, the engineered alpha-NAGAL (which we call alpha-NAGAL(EL)) retains the antigenicity of alpha-NAGAL but has acquired the enzymatic specificity of the alpha-GAL enzyme. Comparison of the crystal structures of the designed enzyme alpha-GAL(SA) to the wild-type enzymes shows that active sites of alpha-GAL(SA) and alpha-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21092187 D.P.Germain (2010).
Fabry disease.
  Orphanet J Rare Dis, 5, 30.  
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