PDBsum entry 4nc5

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protein ligands links
Hydrolase PDB id
Protein chain
354 a.a.
PO4 ×2
Waters ×103
PDB id:
Name: Hydrolase
Title: Human sialidase 2 in complex with 2,3-difluorosialic acid (c intermediate)
Structure: Sialidase-2. Chain: a. Synonym: neu2, cytosolic sialidase, n-acetyl-alpha-neuramin engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: neu2. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.51Å     R-factor:   0.178     R-free:   0.263
Authors: S.Buchini,F.-X.Gallat,I.R.Greig,J.-H.Kim,S.Wakatsuki,L.M.G.C S.G.Withers
Key ref: S.Buchini et al. (2014). Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural insights. Angew Chem Int Ed Engl, 53, 3382-3386. PubMed id: 24591206 DOI: 10.1002/anie.201309675
24-Oct-13     Release date:   06-Nov-13    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9Y3R4  (NEUR2_HUMAN) -  Sialidase-2
380 a.a.
354 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Exo-alpha-sialidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     metabolic process   9 terms 
  Biochemical function     exo-alpha-(2->3)-sialidase activity     6 terms  


DOI no: 10.1002/anie.201309675 Angew Chem Int Ed Engl 53:3382-3386 (2014)
PubMed id: 24591206  
Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural insights.
S.Buchini, F.X.Gallat, I.R.Greig, J.H.Kim, S.Wakatsuki, L.M.Chavas, S.G.Withers.
3-Fluorosialosyl fluorides are inhibitors of sialidases that function by the formation of a long-lived covalent active-site adduct and have potential as therapeutics if made specific for the pathogen sialidase. Surprisingly, human Neu2 and the Trypanosoma cruzi trans-sialidase are inactivated more rapidly by the reagent with an equatorial fluorine at C3 than by its axial epimer, with reactivation following the same pattern. To explore a possible stereoelectronic basis for this, rate constants for spontaneous hydrolysis of the full series of four 3-fluorosialosyl fluorides were measured, and ground-state energies for each computed. The alpha (equatorial) anomeric fluorides hydrolyze more rapidly than their beta anomers, consistent with their higher ground-state energies. However ground-state energies do not explain the relative spontaneous reactivities of the 3-fluoro-epimers. The three-dimensional structures of the two 3-fluoro-sialosyl enzyme intermediates of human Neu2 were solved, revealing key stabilizing interactions between Arg21 and the equatorial, but not the axial, fluorine. Because of changes in geometry these interactions will increase at the transition state, likely explaining the difference in reaction rates.