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Open data
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Basic information
Entry | Database: PDB / ID: 4zuk | ||||||
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Title | Structure ALDH7A1 complexed with NAD+ | ||||||
![]() | Alpha-aminoadipic semialdehyde dehydrogenase | ||||||
![]() | OXIDOREDUCTASE / ALDEHYDE DEHYDROGENASE / NAD / LYSINE CATABOLISM | ||||||
Function / homology | ![]() L-aminoadipate-semialdehyde dehydrogenase / L-aminoadipate-semialdehyde dehydrogenase activity / Choline catabolism / choline catabolic process / betaine-aldehyde dehydrogenase / betaine-aldehyde dehydrogenase (NAD+) activity / Lysine catabolism / cellular aldehyde metabolic process / glycine betaine biosynthetic process from choline / glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity ...L-aminoadipate-semialdehyde dehydrogenase / L-aminoadipate-semialdehyde dehydrogenase activity / Choline catabolism / choline catabolic process / betaine-aldehyde dehydrogenase / betaine-aldehyde dehydrogenase (NAD+) activity / Lysine catabolism / cellular aldehyde metabolic process / glycine betaine biosynthetic process from choline / glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity / aldehyde dehydrogenase (NAD+) / aldehyde dehydrogenase (NAD+) activity / sensory perception of sound / mitochondrial matrix / mitochondrion / extracellular exosome / identical protein binding / nucleus / cytosol Similarity search - Function | ||||||
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Method | ![]() ![]() ![]() | ||||||
![]() | Luo, M. / Tanner, J.J. | ||||||
![]() | ![]() Title: Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1. Authors: Min Luo / John J Tanner / ![]() Abstract: Aldehyde dehydrogenase 7A1 (ALDH7A1) is part of lysine catabolism and catalyzes the NAD(+)-dependent oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Herein, we describe a structural ...Aldehyde dehydrogenase 7A1 (ALDH7A1) is part of lysine catabolism and catalyzes the NAD(+)-dependent oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Herein, we describe a structural study of human ALDH7A1 focused on substrate recognition. Five crystal structures and small-angle X-ray scattering data are reported, including the first crystal structure of any ALDH7 family member complexed with α-aminoadipate. The product binds with the ε-carboxylate in the oxyanion hole, the aliphatic chain packed into an aromatic box, and the distal end of the product anchored by electrostatic interactions with five conserved residues. This binding mode resembles that of glutamate bound to the proline catabolic enzyme ALDH4A1. Analysis of ALDH7A1 and ALDH4A1 structures suggests key interactions that underlie substrate discrimination. Structures of apo ALDH7A1 reveal dramatic conformational differences from the product complex. Product binding is associated with a 16 Å movement of the C-terminus into the active site, which stabilizes the active conformation of the aldehyde substrate anchor loop. The fact that the C-terminus is part of the active site was hitherto unknown. Interestingly, the C-terminus and aldehyde anchor loop are disordered in a new tetragonal crystal form of the apoenzyme, implying that these parts of the enzyme are highly flexible. Our results suggest that the active site of ALDH7A1 is disassembled when the aldehyde site is vacant, and the C-terminus is a mobile element that forms quaternary structural interactions that aid aldehyde binding. These results are relevant to the c.1512delG genetic deletion associated with pyridoxine-dependent epilepsy, which alters the C-terminus of ALDH7A1. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.5 MB | Display | ![]() |
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PDB format | ![]() | 1.2 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 3.2 MB | Display | ![]() |
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Full document | ![]() | 3.2 MB | Display | |
Data in XML | ![]() | 145.1 KB | Display | |
Data in CIF | ![]() | 201.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4zulC ![]() 4zvwC ![]() 4zvxC ![]() 4zvyC ![]() 2j6lS C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 55620.367 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P49419, L-aminoadipate-semialdehyde dehydrogenase, aldehyde dehydrogenase (NAD+), betaine-aldehyde dehydrogenase #2: Chemical | ChemComp-PG4 / #3: Chemical | ChemComp-NAD / #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.24 Å3/Da / Density % sol: 45.05 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: Protein stock solution contained 3 mg/mL ALDH7A1 and 5 mM NAD+. The reservoir contained 0.2 M ammonium sulfate and 20% PEG 3350, 0.1 mM Bis-Tris pH 6.5. PH range: 6.5 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||
Detector | Type: RDI CMOS_8M / Detector: CMOS / Date: Sep 24, 2014 / Details: Taurus-1 detector | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2→62.89 Å / Num. obs: 261450 / % possible obs: 99.5 % / Redundancy: 3.8 % / Biso Wilson estimate: 24.87 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.106 / Rpim(I) all: 0.063 / Net I/σ(I): 12.7 / Num. measured all: 995590 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2J6L Resolution: 2.001→62.89 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 23.15 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 118.85 Å2 / Biso mean: 30.0948 Å2 / Biso min: 12.02 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.001→62.89 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 30
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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