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PDBsum entry 4gqr

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
4gqr
Jmol
Contents
Protein chain
496 a.a.
Ligands
NAG
MYC
Metals
_CA
_CL
Waters ×651
PDB id:
4gqr
Name: Hydrolase/hydrolase inhibitor
Title: Human pancreatic alpha-amylase in complex with myricetin
Structure: Pancreatic alpha-amylase. Chain: a. Fragment: unp residues 16-511. Synonym: pa, 1,4-alpha-d-glucan glucanohydrolase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: amy2a. Expressed in: komagataella pastoris. Expression_system_taxid: 4922
Resolution:
1.20Å     R-factor:   0.180     R-free:   0.198
Authors: L.K.Williams,G.D.Brayer
Key ref: L.K.Williams et al. (2012). Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J Med Chem, 55, 10177-10186. PubMed id: 23050660 DOI: 10.1021/jm301273u
Date:
23-Aug-12     Release date:   24-Oct-12    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04746  (AMYP_HUMAN) -  Pancreatic alpha-amylase
Seq:
Struc:
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.3.2.1.1  - 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   6 terms 
  Biochemical function     catalytic activity     8 terms  

 

 
DOI no: 10.1021/jm301273u J Med Chem 55:10177-10186 (2012)
PubMed id: 23050660  
 
 
Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target.
L.K.Williams, C.Li, S.G.Withers, G.D.Brayer.
 
  ABSTRACT  
 
The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human pancreatic α-amylase. Myricetin binds at the active site and interacts directly with the catalytic residues despite its bulky planar nature. Notably, it reduces the normal conformational flexibility of the adjacent substrate binding cleft. In contrast, bound ethyl caffeate acts by disordering precisely those polypeptide chain segments that make up the active site binding cleft. It also operates from binding sites far removed from the active site, a property not observed in any other class of human α-amylase inhibitor studied to date. Given the current inadequacy of drugs directed at diabetes, the use of optimized flavonols and ethyl caffeates may present an alternative therapeutic route.