7K35

EQADH-NADH-4-METHYLBENZYL ALCOHOL, p21

  • Classification: OXIDOREDUCTASE
  • Organism(s): Equus caballus
  • Mutation(s): No 

  • Deposited: 2020-09-10 Released: 2020-09-23 
  • Deposition Author(s): Plapp, B.V., Ramaswamy, S.
  • Funding Organization(s): National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIH/NIAAA)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.176 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase.

Plapp, B.V.Subramanian, R.

(2021) Arch Biochem Biophys 701: 108825-108825

  • DOI: https://doi.org/10.1016/j.abb.2021.108825
  • Primary Citation of Related Structures:  
    6XT2, 7JQA, 7K35

  • PubMed Abstract: 

    Enzymes typically have high specificity for their substrates, but the structures of substrates and products differ, and multiple modes of binding are observed. In this study, high resolution X-ray crystallography of complexes with NADH and alcohols show alternative modes of binding in the active site. Enzyme crystallized with the good substrates NAD + and 4-methylbenzyl alcohol was found to be an abortive complex of NADH with 4-methylbenzyl alcohol rotated to a "non-productive" mode as compared to the structures that resemble reactive Michaelis complexes with NAD + and 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol. The NADH is formed by reduction of the NAD + with the alcohol during the crystallization. The same structure was also formed by directly crystallizing the enzyme with NADH and 4-methylbenzyl alcohol. Crystals prepared with NAD + and 4-bromobenzyl alcohol also form the abortive complex with NADH. Surprisingly, crystals prepared with NAD + and the strong inhibitor 1H,1H-heptafluorobutanol also had NADH, and the alcohol was bound in two different conformations that illustrate binding flexibility. Oxidation of 2-methyl-2,4-pentanediol during the crystallization apparently led to reduction of the NAD + . Kinetic studies show that high concentrations of alcohols can bind to the enzyme-NADH complex and activate or inhibit the enzyme. Together with previous studies on complexes with NADH and formamide analogues of the carbonyl substrates, models for the Michaelis complexes with NAD + -alcohol and NADH-aldehyde are proposed.


  • Organizational Affiliation

    Department of Biochemistry, The University of Iowa, Iowa City, IA, 52242, USA. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alcohol dehydrogenase E chain
A, B, C, D
374Equus caballusMutation(s): 0 
EC: 1.1.1.1
UniProt
Find proteins for P00327 (Equus caballus)
Explore P00327 
Go to UniProtKB:  P00327
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00327
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAI (Subject of Investigation/LOI)
Query on NAI

Download Ideal Coordinates CCD File 
G [auth A],
K [auth B],
P [auth C],
U [auth D]
1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE
C21 H29 N7 O14 P2
BOPGDPNILDQYTO-NNYOXOHSSA-N
VTG (Subject of Investigation/LOI)
Query on VTG

Download Ideal Coordinates CCD File 
H [auth A],
L [auth B],
Q [auth C],
V [auth D]
(4-methylphenyl)methanol
C8 H10 O
KMTDMTZBNYGUNX-UHFFFAOYSA-N
MRD
Query on MRD

Download Ideal Coordinates CCD File 
M [auth B],
R [auth C]
(4R)-2-METHYLPENTANE-2,4-DIOL
C6 H14 O2
SVTBMSDMJJWYQN-RXMQYKEDSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
I [auth B]
J [auth B]
N [auth C]
E [auth A],
F [auth A],
I [auth B],
J [auth B],
N [auth C],
O [auth C],
S [auth D],
T [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.176 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.22α = 90
b = 180.22β = 106.12
c = 86.86γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIH/NIAAA)United StatesAA00279

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-23
    Type: Initial release
  • Version 1.1: 2021-03-17
    Changes: Database references
  • Version 1.2: 2023-10-18
    Changes: Data collection, Database references, Refinement description