PDBsum entry 1u2y

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Hydrolase PDB id
Protein chain
496 a.a. *
Waters ×206
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: In situ extension as an approach for identifying novel alpha inhibitors, structure containing d-gluconhydroximo-1,5-lact
Structure: Alpha-amylase, pancreatic. Chain: a. Synonym: 1,4-alpha-d-glucan glucanohydrolase, pancreatic al amylase, pa. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: amy2a. Expressed in: pichia pastoris. Expression_system_taxid: 4922
1.95Å     R-factor:   0.167     R-free:   0.198
Authors: S.Numao,C.Li,I.Damager,T.M.Wrodnigg,A.Begum,C.M.Overall,G.D. S.G.Withers
Key ref:
S.Numao et al. (2004). In situ extension as an approach for identifying novel alpha-amylase inhibitors. J Biol Chem, 279, 48282-48291. PubMed id: 15304511 DOI: 10.1074/jbc.M406804200
20-Jul-04     Release date:   07-Sep-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P04746  (AMYP_HUMAN) -  Pancreatic alpha-amylase
511 a.a.
496 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Alpha-amylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endohydrolysis of 1,4-alpha-glucosidic linkages in oligosaccharides and polysaccharides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1074/jbc.M406804200 J Biol Chem 279:48282-48291 (2004)
PubMed id: 15304511  
In situ extension as an approach for identifying novel alpha-amylase inhibitors.
S.Numao, I.Damager, C.Li, T.M.Wrodnigg, A.Begum, C.M.Overall, G.D.Brayer, S.G.Withers.
A new approach for the discovery and subsequent structural elucidation of oligosaccharide-based inhibitors of alpha-amylases based upon autoglucosylation of known alpha-glucosidase inhibitors is presented. This concept, highly analogous to what is hypothesized to occur with acarbose, is demonstrated with the known alpha-glucosidase inhibitor, d-gluconohydroximino-1,5-lactam. This was transformed from an inhibitor of human pancreatic alpha-amylase with a K(i) value of 18 mm to a trisaccharide analogue with a K(i) value of 25 mum. The three-dimensional structure of this complex was determined by x-ray crystallography and represents the first such structure determined with this class of inhibitors in any alpha-glycosidase. This approach to the discovery and structural analysis of amylase inhibitors should be generally applicable to other endoglucosidases and readily adaptable to a high throughput format.
  Selected figure(s)  
Figure 8.
FIG. 8. Stereo drawings illustrating the bound conformations of the inhibitors GHIL (a), GHIL/G3F product (b), and acarbose (c) in the active site of HPA. Only selected active site residues are shown for clarity.
Figure 9.
FIG. 9. Schematic diagrams illustrating the hydrogen bonding interactions ( 3.5 Å) formed in the active site of HPA by GHIL (a), G2-GHIL formed on incubation with GHIL and G3F (b), and acarbose (c). The subsites of HPA occupied by each bound moiety are indicated, and interacting amino acids are designated with their one-letter codes.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 48282-48291) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20302376 I.Damager, S.B.Engelsen, A.Blennow, B.L.Møller, and M.S.Motawia (2010).
First principles insight into the alpha-glucan structures of starch: their synthesis, conformation, and hydration.
  Chem Rev, 110, 2049-2080.  
18214874 C.A.Tarling, K.Woods, R.Zhang, H.C.Brastianos, G.D.Brayer, R.J.Andersen, and S.G.Withers (2008).
The search for novel human pancreatic alpha-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts.
  Chembiochem, 9, 433-438.  
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