2D2X

Crystal structure of 2-deoxy-scyllo-inosose synthase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of 2-deoxy-scyllo-inosose synthase, a key enzyme in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics, in complex with a mechanism-based inhibitor and NAD+

Nango, E.Kumasaka, T.Hirayama, T.Tanaka, N.Eguchi, T.

(2008) Proteins 70: 517-527

  • DOI: https://doi.org/10.1002/prot.21526
  • Primary Citation of Related Structures:  
    2D2X, 2GRU

  • PubMed Abstract: 

    A key enzyme in the biosynthesis of clinically important aminoglycoside antibiotics is 2-deoxy-scyllo-inosose synthase (DOIS), which catalyzes carbocycle formation from D-glucose-6-phosphate to 2-deoxy-scyllo-inosose through a multistep reaction. This reaction mechanism is similar to the catalysis by dehydroquinate synthase (DHQS) of the cyclization of 3-deoxy-D-arabino-heputulosonate-7-phosphate to dehydroquinate in the shikimate pathway, but significant dissimilarity between these enzymes is also known, particularly in the stereochemistry of the phosphate elimination reaction and the cyclization. Here, the crystal structures of DOIS from Bacillus circulans and its complex with the substrate analog inhibitor carbaglucose-6-phosphate, NAD+, and Co2+ have been determined to provide structural insights into the reaction mechanism. The complex structure shows that an active site exists between the N-terminal and C-terminal domains and that the inhibitor coordinates a cobalt ion in this site. Two subunits exist as a dimer in the asymmetric unit. The two active sites of the dimer were observed to be different. One contains a dephosphorylated compound derived from the inhibitor and the other includes the inhibitor without change. The present study suggested that phosphate elimination proceeds through syn-elimination assisted by Glu 243 and the aldol condensation proceeds via a boat conformation. Also discussed are significant similarities and dissimilarities between DOIS and DHQS, particularly in terms of the structure at the active site and the reaction mechanism.


  • Organizational Affiliation

    Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2-deoxy-scyllo-inosose synthase
A, B
368Niallia circulansMutation(s): 0 
EC: 4.2.3
UniProt
Find proteins for Q9S5E2 (Niallia circulans)
Explore Q9S5E2 
Go to UniProtKB:  Q9S5E2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9S5E2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B],
K [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
SO3
Query on SO3

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B]
SULFITE ION
O3 S
LSNNMFCWUKXFEE-UHFFFAOYSA-L
CO
Query on CO

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A],
H [auth B]
COBALT (II) ION
Co
XLJKHNWPARRRJB-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.207 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.51α = 90
b = 70.35β = 117.84
c = 82.984γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
MLPHAREphasing
CNSrefinement
CCP4data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-03
    Type: Initial release
  • Version 1.1: 2008-04-22
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance