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PDBsum entry 4sli

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Enzyme PDB id
4sli
Jmol
Contents
Protein chain
679 a.a. *
Ligands
CNP
Waters ×560
* Residue conservation analysis
PDB id:
4sli
Name: Enzyme
Title: Leech intramolecular trans-sialidase complexed with 2- propenyl-neu5ac, an inactive substrate analogue
Structure: Intramolecular trans-sialidase. Chain: a. Fragment: devoid of n-terminal 28 residues. Engineered: yes
Source: Macrobdella decora. North american leech. Organism_taxid: 6405. Gene: t7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: de3.
Resolution:
1.80Å     R-factor:   0.189     R-free:   0.229
Authors: Y.Luo,S.C.Li,Y.T.Li,M.Luo
Key ref:
Y.Luo et al. (1999). The 1.8 A structures of leech intramolecular trans-sialidase complexes: evidence of its enzymatic mechanism. J Mol Biol, 285, 323-332. PubMed id: 9878409 DOI: 10.1006/jmbi.1998.2345
Date:
04-Oct-98     Release date:   25-May-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q27701  (NANL_MACDE) -  Anhydrosialidase
Seq:
Struc:
 
Seq:
Struc:
762 a.a.
679 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.2.15  - Anhydrosialidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Anhydrosialidase
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     metabolic process   3 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
DOI no: 10.1006/jmbi.1998.2345 J Mol Biol 285:323-332 (1999)
PubMed id: 9878409  
 
 
The 1.8 A structures of leech intramolecular trans-sialidase complexes: evidence of its enzymatic mechanism.
Y.Luo, S.C.Li, Y.T.Li, M.Luo.
 
  ABSTRACT  
 
Intramolecular trans-sialidase from leech (Macrobdella decora) is the first member of the sialidase superfamily found to exhibit strict specificity towards the cleavage of terminal Neu5Acalpha2-->3Gal linkage in sialoglycoconjugates. Its release of 2,7-anhydro-Neu5Ac instead of Neu5Ac indicates that it catalyzes an intramolecular trans-sialosyl reaction. Crystal structures of its complexes with an inactive substrate analogue 2-propenyl-Neu5Ac, and with the product 2,7-anhydro-Neu5Ac, have been determined to 1.8 A resolution. The boat conformation of the pyranose observed in the complexes supports the proposed enzymatic mechanism that O7 of an axial 6-glycerol group attacks the positively charged C2 of the intermediate. A generalized mechanism is proposed for the sialidase superfamily.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. F[o] - F[c] maps contoured at 2.0 s for the leech IT-sialidase complexes with (a) inactive substrate analogue 2-propenyl-Neu5Ac (the terminal carbon in the 2-propenyl is not shown). There is no density for the two terminal carbon groups in 2-propenyl. In addition, 6-glycerol appears disordered with a bulk density. (b) Product 2,7-anhydro-Neu5Ac; (c) also product 2,7-anhydro-Neu5Ac, soaked with substrate 3'-sialyllactose.
Figure 6.
Figure 6. Alternate enzymatic pathways by hydrolytic sialidases/neuraminidases, trans-sialidases, and IT-sialidases. The favored substrate conformation (left) in the active site is always a boat conformation. The differences between each enzymatic mechanism are the nucleophilic attacking atoms. These are activated water molecule in sialidase, the 3-hydroxyl of the galactose intrans-sialidase, and the 7-hydroxyl of the substrate sialic acid in IT-sialidase. The proximity of the hydroxyl groups is enforced by the conformation restraints imposed by the active site.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 285, 323-332) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
16510969 F.Fabiola, A.Korostelev, and M.S.Chapman (2006).
Bias in cross-validated free R factors: mitigation of the effects of non-crystallographic symmetry.
  Acta Crystallogr D Biol Crystallogr, 62, 227-238.  
14730352 C.P.Chiu, A.G.Watts, L.L.Lairson, M.Gilbert, D.Lim, W.W.Wakarchuk, S.G.Withers, and N.C.Strynadka (2004).
Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
  Nat Struct Mol Biol, 11, 163-170.
PDB codes: 1ro7 1ro8
14580216 J.N.Watson, V.Dookhun, T.J.Borgford, and A.J.Bennet (2003).
Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase.
  Biochemistry, 42, 12682-12690.  
12732625 M.Wimmerova, E.Mitchell, J.F.Sanchez, C.Gautier, and A.Imberty (2003).
Crystal structure of fungal lectin: six-bladed beta-propeller fold and novel fucose recognition mode for Aleuria aurantia lectin.
  J Biol Chem, 278, 27059-27067.
PDB code: 1ofz
12419220 A.Buschiazzo, M.F.Amaya, M.L.Cremona, A.C.Frasch, and P.M.Alzari (2002).
The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis.
  Mol Cell, 10, 757-768.
PDB codes: 1mr5 1ms0 1ms1 1ms3 1ms4 1ms5 1ms8 1ms9
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.