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PDBsum entry 1odu

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Hydrolase PDB id
1odu
Jmol
Contents
Protein chains
422 a.a. *
Ligands
FUL ×2
* Residue conservation analysis
PDB id:
1odu
Name: Hydrolase
Title: Crystal structure of thermotoga maritima alpha-fucosidase in complex with fucose
Structure: Putative alpha-l-fucosidase. Chain: a, b. Engineered: yes. Other_details: orf tm0306
Source: Thermotoga maritima. Organism_taxid: 243274. Strain: msb8. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Hexamer (from PDB file)
Resolution:
2.80Å     R-factor:   0.203     R-free:   0.230
Authors: G.Sulzenbacher,C.Bignon,Y.Bourne,B.Henrissat
Key ref:
G.Sulzenbacher et al. (2004). Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the catalytic mechanism and the molecular basis for fucosidosis. J Biol Chem, 279, 13119-13128. PubMed id: 14715651 DOI: 10.1074/jbc.M313783200
Date:
14-Mar-03     Release date:   15-Jan-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9WYE2  (Q9WYE2_THEMA) -  Alpha-L-fucosidase
Seq:
Struc:
449 a.a.
422 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     carbohydrate metabolic process   2 terms 
  Biochemical function     alpha-L-fucosidase activity     1 term  

 

 
DOI no: 10.1074/jbc.M313783200 J Biol Chem 279:13119-13128 (2004)
PubMed id: 14715651  
 
 
Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the catalytic mechanism and the molecular basis for fucosidosis.
G.Sulzenbacher, C.Bignon, T.Nishimura, C.A.Tarling, S.G.Withers, B.Henrissat, Y.Bourne.
 
  ABSTRACT  
 
Fucosylated glycoconjugates are involved in numerous biological events, and alpha-l-fucosidases, the enzymes responsible for their processing, are therefore of crucial importance. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterized by rapid neurodegeneration, resulting in severe mental and motor deterioration. To gain insight into alpha-l-fucosidase function at the molecular level, we have determined the crystal structure of Thermotoga maritima alpha-l-fucosidase. This enzyme assembles as a hexamer and displays a two-domain fold, composed of a catalytic (beta/alpha)(8)-like domain and a C-terminal beta-sandwich domain. The structures of an enzyme-product complex and of a covalent glycosyl-enzyme intermediate, coupled with kinetic and mutagenesis studies, allowed us to identify the catalytic nucleophile, Asp(244), and the Brønsted acid/base, Glu(266). Because T. maritima alpha-l-fucosidase occupies a unique evolutionary position, being far more closely related to the mammalian enzymes than to any other prokaryotic homolog, a structural model of the human enzyme was built to document the structural consequences of the genetic mutations associated with fucosidosis.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The catalytic pocket of TM aFuc. Shown are stereo pairs of the 2F[o] - 2F[c] electron density maps for the fucose complex (A) and the fucosyl-enzyme intermediate (B) at 2.8 and 2.25 Å, respectively. Phases were calculated prior to incorporation of the ligand in the refinement, and the maps were contoured at 1.0 . Also shown is a schematic summarizing the interactions between TM aFuc and fucose (C). The ligand is shown in boldface, hydrogen bonds are shown as dashed lines, and van der Waals contacts are shown as pink dotted lines.
Figure 2.
FIG. 2. Overall view of TM aFuc. A, stereo ribbon diagram colored in a gradient along the TM aFuc amino acid sequence, from the N terminus (blue) to the C terminus (red). Secondary structure elements corresponding to the classical ( / )[8]-fold are indicated. The catalytic nucleophile Asp224 and the acid/base Glu266 are shown in ball-and-stick presentation, with carbon atoms colored gray and oxygen atoms colored red. B, the hexameric assembly of TM aFuc, as seen from the top (left) and rotated by 90° (right). For clarity, the trimers composing the hexamer are colored magenta and white, and one trimer is highlighted by a transparent surface representation. Bound fucose molecules are shown in green.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 13119-13128) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19940122 A.I.Guce, N.E.Clark, E.N.Salgado, D.R.Ivanen, A.A.Kulminskaya, H.Brumer, and S.C.Garman (2010).
Catalytic mechanism of human alpha-galactosidase.
  J Biol Chem, 285, 3625-3632.
PDB codes: 3hg2 3hg3 3hg4 3hg5
20665773 A.Lammerts van Bueren, S.D.Popat, C.H.Lin, and G.J.Davies (2010).
Structural and thermodynamic analyses of α-L-fucosidase inhibitors.
  Chembiochem, 11, 1971-1974.
PDB codes: 2xib 2xii
19225683 A.Caravano, R.A.Field, J.M.Percy, G.Rinaudo, R.Roig, and K.Singh (2009).
Developing an asymmetric, stereodivergent route to selected 6-deoxy-6-fluoro-hexoses.
  Org Biomol Chem, 7, 996.  
19875083 B.Cobucci-Ponzano, F.Conte, E.Bedini, M.M.Corsaro, M.Parrilli, G.Sulzenbacher, A.Lipski, F.Dal Piaz, L.Lepore, M.Rossi, and M.Moracci (2009).
beta-Glycosyl azides as substrates for alpha-glycosynthases: preparation of efficient alpha-L-fucosynthases.
  Chem Biol, 16, 1097-1108.
PDB code: 2wsp
19520709 H.Ashida, A.Miyake, M.Kiyohara, J.Wada, E.Yoshida, H.Kumagai, T.Katayama, and K.Yamamoto (2009).
Two distinct alpha-L-fucosidases from Bifidobacterium bifidum are essential for the utilization of fucosylated milk oligosaccharides and glycoconjugates.
  Glycobiology, 19, 1010-1017.  
19579240 J.Calveras, M.Egido-Gabás, L.Gómez, J.Casas, T.Parella, J.Joglar, J.Bujons, and P.Clapés (2009).
Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties.
  Chemistry, 15, 7310-7328.  
18615268 A.Aguirre-Valderrama, and J.A.Dobado (2008).
CAL3JHH: a Java program to calculate the vicinal coupling constants (3J H,H) of organic molecules.
  J Comput Aided Mol Des, 22, 907-914.  
17687508 B.Cobucci-Ponzano, F.Conte, M.Rossi, and M.Moracci (2008).
The alpha-L: -fucosidase from Sulfolobus solfataricus.
  Extremophiles, 12, 61-68.  
18558099 D.J.Vocadlo, and G.J.Davies (2008).
Mechanistic insights into glycosidase chemistry.
  Curr Opin Chem Biol, 12, 539-555.  
18076078 N.S.Kumar, D.A.Kuntz, X.Wen, B.M.Pinto, and D.R.Rose (2008).
Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: the role of water in inhibitor binding.
  Proteins, 71, 1484-1496.
PDB codes: 2ow6 2ow7
16920738 B.Cobucci-Ponzano, F.Conte, D.Benelli, P.Londei, A.Flagiello, M.Monti, P.Pucci, M.Rossi, and M.Moracci (2006).
The gene of an archaeal alpha-L-fucosidase is expressed by translational frameshifting.
  Nucleic Acids Res, 34, 4258-4268.  
16233842 T.Miura, K.Okamoto, and H.Yanase (2005).
Purification and characterization of extracellular 1,2-alpha-L-fucosidase from Bacillus cereus.
  J Biosci Bioeng, 99, 629-635.  
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.