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PDBsum entry 1ocq

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protein ligands links
Hydrolase PDB id
1ocq
Jmol PyMol
Contents
Protein chain
300 a.a. *
Ligands
IFM-BGC
GOL ×2
SO4
Waters ×445
* Residue conservation analysis
PDB id:
1ocq
Name: Hydrolase
Title: Complex of the endoglucanase cel5a from bacillus agaradhearans at 1.08 angstrom resolution with cellobio-derived isofagomine
Structure: Endoglucanase 5a. Chain: a. Fragment: catalytic core domain only, residues 27-329. Synonym: endo-1,4-beta-glucanase, alkaline cellulase, cel5a. Engineered: yes
Source: Bacillus agaradhaerens. Organism_taxid: 76935. Expressed in: bacillus subtilis. Expression_system_taxid: 1423.
Resolution:
1.08Å     R-factor:   0.115     R-free:   0.127
Authors: A.Varrot,J.M.Macdonald,R.V.Stick,S.G.Withers,G.J.Davies
Key ref: A.Varrot et al. (2003). Direct observation of the protonation state of an imino sugar glycosidase inhibitor upon binding. J Am Chem Soc, 125, 7496-7497. PubMed id: 12812472 DOI: 10.1021/ja034917k
Date:
09-Feb-03     Release date:   26-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O85465  (GUN5_BACAG) -  Endoglucanase 5A
Seq:
Struc:
400 a.a.
300 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.4  - Cellulase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endohydrolysis of 1,4-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     hydrolase activity, hydrolyzing O-glycosyl compounds     1 term  

 

 
DOI no: 10.1021/ja034917k J Am Chem Soc 125:7496-7497 (2003)
PubMed id: 12812472  
 
 
Direct observation of the protonation state of an imino sugar glycosidase inhibitor upon binding.
A.Varrot, C.A.Tarling, J.M.Macdonald, R.V.Stick, D.L.Zechel, S.G.Withers, G.J.Davies.
 
  ABSTRACT  
 
Glycosidases are some of the most ubiquitous enzyme in nature. Their biological significance, coupled to their enormous catalytic prowess derived from tight binding of the transition state, is reflected in their importance as therapeutic targets. Many glycosidase inhibitors are known. Imino sugars are often potent inhibitors, yet many facets of their mode of action, such as their degree, if any, of transition-state "mimicry" and their protonation state when bound to the target glycosidase remain unclear. Atomic resolution analysis of the endoglucanase, Cel5A, in complex with a cellobio-derived isofagomine in conjunction with the pH dependence of Ki and kcat/KM reveals that this compound binds as a protonated sugar. Surprisingly, both the enzymatic nucleophile and the acid/base are unprotonated in the complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20066263 T.M.Gloster, and G.J.Davies (2010).
Glycosidase inhibition: assessing mimicry of the transition state.
  Org Biomol Chem, 8, 305-320.  
19543714 H.Schagerlöf, C.Nilsson, L.Gorton, F.Tjerneld, H.Stålbrand, and A.Cohen (2009).
Use of 18O water and ESI-MS detection in subsite characterisation and investigation of the hydrolytic action of an endoglucanase.
  Anal Bioanal Chem, 394, 1977-1984.  
19532990 M.Aguilar-Moncayo, T.M.Gloster, J.P.Turkenburg, M.I.García-Moreno, C.Ortiz Mellet, G.J.Davies, and J.M.García Fernández (2009).
Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring.
  Org Biomol Chem, 7, 2738-2747.
PDB codes: 2wbg 2wc3 2wc4
18074341 A.D.Hill, and P.J.Reilly (2008).
A Gibbs free energy correlation for automated docking of carbohydrates.
  J Comput Chem, 29, 1131-1141.  
18256510 H.Saino, M.Mizutani, J.Hiratake, and K.Sakata (2008).
Expression and biochemical characterization of beta-primeverosidase and application of beta-primeverosylamidine to affinity purification.
  Biosci Biotechnol Biochem, 72, 376-383.  
16787095 S.P.Kawatkar, D.A.Kuntz, R.J.Woods, D.R.Rose, and G.J.Boons (2006).
Structural basis of the inhibition of Golgi alpha-mannosidase II by mannostatin A and the role of the thiomethyl moiety in ligand-protein interactions.
  J Am Chem Soc, 128, 8310-8319.
PDB codes: 2f7o 2f7p
16628756 T.M.Gloster, R.Madsen, and G.J.Davies (2006).
Dissection of conformationally restricted inhibitors binding to a beta-glucosidase.
  Chembiochem, 7, 738-742.
PDB codes: 2cbu 2cbv
15987675 E.J.Taylor, A.Goyal, C.I.Guerreiro, J.A.Prates, V.A.Money, N.Ferry, C.Morland, A.Planas, J.A.Macdonald, R.V.Stick, H.J.Gilbert, C.M.Fontes, and G.J.Davies (2005).
How family 26 glycoside hydrolases orchestrate catalysis on different polysaccharides: structure and activity of a Clostridium thermocellum lichenase, CtLic26A.
  J Biol Chem, 280, 32761-32767.
PDB codes: 2bv9 2bvd
15853815 J.Jänis, J.Hakanpää, N.Hakulinen, F.M.Ibatullin, A.Hoxha, P.J.Derrick, J.Rouvinen, and P.Vainiotalo (2005).
Determination of thioxylo-oligosaccharide binding to family 11 xylanases using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and X-ray crystallography.
  FEBS J, 272, 2317-2333.
PDB code: 1xnk
14597633 M.Hrmova, R.De Gori, B.J.Smith, A.Vasella, J.N.Varghese, and G.B.Fincher (2004).
Three-dimensional structure of the barley beta-D-glucan glucohydrolase in complex with a transition state mimic.
  J Biol Chem, 279, 4970-4980.
PDB code: 1lq2
15356002 T.M.Gloster, J.M.Macdonald, C.A.Tarling, R.V.Stick, S.G.Withers, and G.J.Davies (2004).
Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases.
  J Biol Chem, 279, 49236-49242.
PDB codes: 1w3j 1w3k 1w3l
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.

 

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