4X0T

Structure ALDH7A1 inactivated by 4-diethylaminobenzaldehyde and complexed with NAD+

PDB DOI: https://doi.org/10.2210/pdb4X0T/pdb

Classification: oxidoreductase/oxidoreductase inhibitor
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2014-11-23 Released: 2015-01-14
Deposition Author(s): Luo, M., Tanner, J.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.235
R-Value Work: 0.180
R-Value Observed: 0.183

Starting Model: experimental
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Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Diethylaminobenzaldehyde Is a Covalent, Irreversible Inactivator of ALDH7A1.

Luo, M., Gates, K.S., Henzl, M.T., Tanner, J.J.

(2015) ACS Chem Biol 10: 693-697

PubMed: 25554827 Search on PubMed
DOI: https://doi.org/10.1021/cb500977q
Primary Citation of Related Structures:
4X0T, 4X0U

PubMed Abstract:
There is growing interest in aldehyde dehydrogenases (ALDHs) because of their overexpression in cancer stem cells and the ability to mediate resistance to cancer drugs. Here, we report the first crystal structure of an aldehyde dehydrogenase complexed with the inhibitor 4-diethylaminobenzaldehyde (DEAB). Contrary to the widely held belief that DEAB is a reversible inhibitor of ALDHs, we show that DEAB irreversibly inactivates ALDH7A1 via formation of a stable, covalent acyl-enzyme species.

Organizational Affiliation

†Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.

Macromolecule Content

Total Structure Weight: 225.84 kDa
Atom Count: 15,675
Modelled Residue Count: 2,035
Deposited Residue Count: 2,052
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Alpha-aminoadipic semialdehyde dehydrogenase	A, B, C, D	513	Homo sapiens	Mutation(s): 0 Gene Names: ALDH7A1, ATQ1 EC: 1.2.1.31 (PDB Primary Data), 1.2.1.3 (PDB Primary Data), 1.2.1.8 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P49419 (Homo sapiens) Explore P49419 Go to UniProtKB: P49419
PHAROS: P49419 GTEx: ENSG00000164904
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P49419
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAD Query on NAD Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain I [auth C] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain I [auth C] MOL2 format, chain K [auth D] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B] mmCIF format, chain I [auth C] mmCIF format, chain K [auth D]	E [auth A], G [auth B], I [auth C], K [auth D]	NICOTINAMIDE-ADENINE-DINUCLEOTIDE C₂₁ H₂₇ N₇ O₁₄ P₂ BAWFJGJZGIEFAR-NNYOXOHSSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D]
3W9 Query on 3W9 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain L [auth D] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B] mmCIF format, chain J [auth C] mmCIF format, chain L [auth D]	F [auth A], H [auth B], J [auth C], L [auth D]	4-(diethylamino)benzaldehyde C₁₁ H₁₅ N O MNFZZNNFORDXSV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.235
R-Value Work: 0.180
R-Value Observed: 0.183
Space Group: I 4 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 160.263	α = 90
b = 160.263	β = 90
c = 320.482	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data scaling
Aimless	data scaling
PDB_EXTRACT	data extraction
PHASER	phasing
XDS	data reduction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2015-01-14

Deposition Author(s):

Luo, M.

Tanner, J.J.

Revision History (Full details and data files)

Version 1.0: 2015-01-14
Type: Initial release
Version 1.1: 2015-04-01
Changes: Database references
Version 1.2: 2017-11-22
Changes: Derived calculations, Refinement description, Source and taxonomy
Version 1.3: 2023-09-27
Changes: Data collection, Database references, Refinement description
Version 1.4: 2024-10-23
Changes: Structure summary