PDBsum entry 1adb

Oxidoreductase (NAD(a)-choh(d))

PDB id: 1adb

Contents

Protein chains

374 a.a. *

Ligands

CND ×2

EOH ×2

Metals

_ZN ×4

Waters ×264

* Residue conservation analysis

PDB id:

1adb

Name:

Oxidoreductase (NAD(a)-choh(d))

Title:

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

Structure:

Alcohol dehydrogenase. Chain: a, b. Engineered: yes

Source:

Equus caballus. Horse. Organism_taxid: 9796

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.180

Authors:

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

Key ref:

H.Li et al. (1994). Crystallographic studies of isosteric NAD analogues bound to alcohol dehydrogenase: specificity and substrate binding in two ternary complexes. Biochemistry, 33, 11734-11744. PubMed id: 7918390 DOI: 10.1021/bi00205a009

Date:

13-Dec-93 Release date: 03-Jun-95

Protein chains

P00327  (ADH1E_HORSE) -  Alcohol dehydrogenase E chain from Equus caballus

Seq: 375 a.a.

Struc: 374 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.1 - alcohol dehydrogenase.
• Reaction:
  1. a primary alcohol + NAD⁺ = an aldehyde + NADH + H⁺
  2. a secondary alcohol + NAD⁺ = a ketone + NADH + H⁺

primary alcohol (Bound ligand (Het Group name = EOH) matches with 50.00% similarity) + NAD(+) (Bound ligand (Het Group name = CND) matches with 66.04% similarity) = aldehyde + NADH + H(+)

secondary alcohol (Bound ligand (Het Group name = EOH) matches with 40.00% similarity) + NAD(+) (Bound ligand (Het Group name = CND) matches with 66.04% similarity) = ketone + NADH + H(+)

• Cofactor: Zn(2+) or Fe cation

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi00205a009

Biochemistry 33:11734-11744 (1994)

PubMed id: 7918390

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

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

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.