1ADC

CRYSTALLOGRAPHIC STUDIES OF ISOSTERIC NAD ANALOGUES BOUND TO ALCOHOL DEHYDROGENASE: SPECIFICITY AND SUBSTRATE BINDING IN TWO TERNARY COMPLEXES


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystallographic studies of isosteric NAD analogues bound to alcohol dehydrogenase: specificity and substrate binding in two ternary complexes.

Li, H.Hallows, W.H.Punzi, J.S.Pankiewicz, K.W.Watanabe, K.A.Goldstein, B.M.

(1994) Biochemistry 33: 11734-11744

  • DOI: https://doi.org/10.1021/bi00205a009
  • Primary Citation of Related Structures:  
    1ADB, 1ADC

  • PubMed Abstract: 

    CNAD (5-beta-D-ribofuranosylnicotinamide adenine dinucleotide) is an isosteric C-glycosidic analogue of NAD(H) containing a neutral pyridine ring. CPAD (5-beta-D-ribofuranosylpicolinamide adenine dinucleotide) is a closely related pyridine-containing analogue with the pyridine nitrogen on the opposite side of the ring. CNAD is a potent and specific inhibitor of horse liver alcohol dehydrogenase (LADH), binding with a dissociation constant in the nanomolar range. CPAD binds LADH with an affinity comparable to that of NAD. Crystal structures of CNAD and CPAD bound to LADH are presented at 2.4 and 2.7 A, respectively. The two complexes are isomorphous, crystallizing in the triclinic system with cell dimensions different from those seen in previous ternary LADH complexes. Structures were solved using the molecular replacement method and refined to crystallographic R values of 18% (CNAD) and 17% (CPAD). Both inhibitors bind to the "closed" form of LADH in the normal cofactor-binding cleft. The conformation of LADH-bound CPAD closely mimics that of LADH-bound NAD(H). The data suggest that alcohol substrate binds directly to the catalytic zinc atom. In the CNAD complex, the pyridine nitrogen replaces alcohol as the fourth coordination ligand to the active site zinc atom, while all other polar interactions remain the same as those of bound NAD(H). The zinc-nitrogen ligand explains the high affinity of CNAD for LADH.


  • Organizational Affiliation

    Department of Biophysics, University of Rochester Medical Center, New York 14642.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ALCOHOL DEHYDROGENASE
A, B
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.9α = 103.1
b = 44.8β = 87.8
c = 93γ = 70.4
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-06-03
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-11-29
    Changes: Derived calculations, Other
  • Version 1.4: 2024-02-07
    Changes: Data collection, Database references, Derived calculations