1U30

In situ extension as an approach for identifying novel alpha-amylase inhibitors, structure containing maltosyl-alpha (1,4)-D-gluconhydroximo-1,5-lactam


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

In Situ Extension as an Approach for Identifying Novel alpha-Amylase Inhibitors.

Numao, S.Damager, I.Li, C.Wrodnigg, T.M.Begum, A.Overall, C.M.Brayer, G.D.Withers, S.G.

(2004) J Biol Chem 279: 48282-48291

  • DOI: https://doi.org/10.1074/jbc.M406804200
  • Primary Citation of Related Structures:  
    1U2Y, 1U30, 1U33

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-amylase, pancreatic496Homo sapiensMutation(s): 0 
Gene Names: AMY2A
EC: 3.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P04746 (Homo sapiens)
Explore P04746 
Go to UniProtKB:  P04746
PHAROS:  P04746
GTEx:  ENSG00000243480 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04746
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LAG
Query on LAG

Download Ideal Coordinates CCD File 
C [auth A]MALTOSYL-ALPHA (1,4)-(Z,3S,4S,5R,6R)-3,4,5-TRIHYDROXY-6-HYDROXYMETHYL-PIPERIDIN-2-ONE OXIME
C18 H32 N2 O15
AHRWQUNEPBVNOT-IVJVVCOPSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
B [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOX
Query on GOX

Download Ideal Coordinates CCD File 
F [auth A](2S,3S,4R,5R)-6-(HYDROXYAMINO)-2-(HYDROXYMETHYL)-2,3,4,5-TETRAHYDROPYRIDINE-3,4,5-TRIOL
C6 H12 N2 O5
VBXHGXTYZGYTQG-SQOUGZDYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
D [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
A
L-PEPTIDE LINKINGC5 H7 N O3GLN
Binding Affinity Annotations 
IDSourceBinding Affinity
GOX Binding MOAD:  1U30 Ki: 1.80e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.26α = 90
b = 68.63β = 90
c = 131.4γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-09-07
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2018-10-03
    Changes: Advisory, Data collection
  • Version 2.0: 2019-12-25
    Changes: Database references, Derived calculations, Polymer sequence
  • Version 2.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 2.2: 2020-11-11
    Changes: Structure summary