2J6L

Structure of aminoadipate-semialdehyde dehydrogenase

PDB DOI: https://doi.org/10.2210/pdb2J6L/pdb

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

Deposited: 2006-09-29 Released: 2006-10-12
Deposition Author(s): Bunkoczi, G., Guo, K., Debreczeni, J.E., Smee, C., Arrowsmith, C., Edwards, A., Sundstrom, M., Weigelt, J., von Delft, F., Oppermann, U.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.30 Å
R-Value Free: 0.189
R-Value Work: 0.137
R-Value Observed: 0.140

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Aldehyde Dehydrogenase 7A1 (Aldh7A1) is a Novel Enzyme Involved in Cellular Defense Against Hyperosmotic Stress.

Brocker, C., Lassen, N., Estey, T., Pappa, A., Cantore, M., Orlova, V.V., Chavakis, T., Kavanagh, K.L., Oppermann, U., Vasiliou, V.

(2010) J Biol Chem 285: 18452

PubMed: 20207735 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1074/jbc.M109.077925
Primary Citation of Related Structures:
2J6L

PubMed Abstract:
Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese hamster ovary cells attenuated osmotic stress-induced apoptosis caused by increased extracellular concentrations of sucrose or sodium chloride. Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate specificities. Tissue distribution studies in mice showed the highest expression of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse cDNA sequences revealed mitochondrial and cytosolic transcripts that are differentially expressed in a tissue-specific manner in mice. In conclusion, ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes.

Organizational Affiliation

Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado 80045, USA.

Macromolecule Content

Total Structure Weight: 440.06 kDa
Atom Count: 36,104
Modelled Residue Count: 3,979
Deposited Residue Count: 4,000
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
ALDEHYDE DEHYDROGENASE FAMILY 7 MEMBER A1	A, B, C, D, E A, B, C, D, E, F, G, H	500	Homo sapiens	Mutation(s): 0 EC: 1.2.1.3
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 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAI Query on NAI Download Ideal Coordinates CCD File SDF format, chain EA [auth F] SDF format, chain HA [auth G] SDF format, chain I [auth A] SDF format, chain KA [auth H] SDF format, chain M [auth B] SDF format, chain S [auth C] SDF format, chain W [auth D] SDF format, chain Z [auth E] MOL2 format, chain EA [auth F] MOL2 format, chain HA [auth G] MOL2 format, chain I [auth A] MOL2 format, chain KA [auth H] MOL2 format, chain M [auth B] MOL2 format, chain S [auth C] MOL2 format, chain W [auth D] MOL2 format, chain Z [auth E]	EA [auth F] HA [auth G] I [auth A] KA [auth H] M [auth B] EA [auth F], HA [auth G], I [auth A], KA [auth H], M [auth B], S [auth C], W [auth D], Z [auth E]	1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE C₂₁ H₂₉ N₇ O₁₄ P₂ BOPGDPNILDQYTO-NNYOXOHSSA-N		Interactions Focus chain EA [auth F] Focus chain HA [auth G] Focus chain I [auth A] Focus chain KA [auth H] Focus chain M [auth B] Focus chain S [auth C] Focus chain W [auth D] Focus chain Z [auth E] Interactions & Density Focus chain EA [auth F] Focus chain HA [auth G] Focus chain I [auth A] Focus chain KA [auth H] Focus chain M [auth B] Focus chain S [auth C] Focus chain W [auth D] Focus chain Z [auth E]
BR Query on BR Download Ideal Coordinates CCD File SDF format, chain AA [auth E] SDF format, chain BA [auth E] SDF format, chain CA [auth E] SDF format, chain FA [auth F] SDF format, chain IA [auth G] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain LA [auth H] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain R [auth B] SDF format, chain T [auth C] SDF format, chain V [auth C] SDF format, chain X [auth D] MOL2 format, chain AA [auth E] MOL2 format, chain BA [auth E] MOL2 format, chain CA [auth E] MOL2 format, chain FA [auth F] MOL2 format, chain IA [auth G] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain LA [auth H] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain R [auth B] MOL2 format, chain T [auth C] MOL2 format, chain V [auth C] MOL2 format, chain X [auth D]	AA [auth E] BA [auth E] CA [auth E] FA [auth F] IA [auth G] AA [auth E], BA [auth E], CA [auth E], FA [auth F], IA [auth G], J [auth A], K [auth A], LA [auth H], N [auth B], O [auth B], P [auth B], R [auth B], T [auth C], V [auth C], X [auth D]	BROMIDE ION Br CPELXLSAUQHCOX-UHFFFAOYSA-M		Interactions Focus chain AA [auth E] Focus chain BA [auth E] Focus chain CA [auth E] Focus chain FA [auth F] Focus chain IA [auth G] Focus chain J [auth A] Focus chain K [auth A] Focus chain LA [auth H] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain R [auth B] Focus chain T [auth C] Focus chain V [auth C] Focus chain X [auth D] Interactions & Density Focus chain AA [auth E] Focus chain BA [auth E] Focus chain CA [auth E] Focus chain FA [auth F] Focus chain IA [auth G] Focus chain J [auth A] Focus chain K [auth A] Focus chain LA [auth H] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain R [auth B] Focus chain T [auth C] Focus chain V [auth C] Focus chain X [auth D]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain DA [auth E] SDF format, chain GA [auth F] SDF format, chain JA [auth G] SDF format, chain L [auth A] SDF format, chain MA [auth H] SDF format, chain Q [auth B] SDF format, chain U [auth C] SDF format, chain Y [auth D] MOL2 format, chain DA [auth E] MOL2 format, chain GA [auth F] MOL2 format, chain JA [auth G] MOL2 format, chain L [auth A] MOL2 format, chain MA [auth H] MOL2 format, chain Q [auth B] MOL2 format, chain U [auth C] MOL2 format, chain Y [auth D]	DA [auth E] GA [auth F] JA [auth G] L [auth A] MA [auth H] DA [auth E], GA [auth F], JA [auth G], L [auth A], MA [auth H], Q [auth B], U [auth C], Y [auth D]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain DA [auth E] Focus chain GA [auth F] Focus chain JA [auth G] Focus chain L [auth A] Focus chain MA [auth H] Focus chain Q [auth B] Focus chain U [auth C] Focus chain Y [auth D] Interactions & Density Focus chain DA [auth E] Focus chain GA [auth F] Focus chain JA [auth G] Focus chain L [auth A] Focus chain MA [auth H] Focus chain Q [auth B] Focus chain U [auth C] Focus chain Y [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.30 Å
R-Value Free: 0.189
R-Value Work: 0.137
R-Value Observed: 0.140
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 155.289	α = 90
b = 162.326	β = 94.17
c = 159.016	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-10-12

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2006-10-12
Type: Initial release
Version 1.1: 2015-05-20
Changes: Database references, Derived calculations, Non-polymer description, Other, Source and taxonomy, Structure summary, Version format compliance
Version 1.2: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description

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Help and Resources

2J6L

Structure of aminoadipate-semialdehyde dehydrogenase

Aldehyde Dehydrogenase 7A1 (Aldh7A1) is a Novel Enzyme Involved in Cellular Defense Against Hyperosmotic Stress.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)