+Open data
-Basic information
Entry | Database: PDB / ID: 4zvw | ||||||
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Title | Structure of apo human ALDH7A1 in space group C2 | ||||||
Components | Alpha-aminoadipic semialdehyde dehydrogenase | ||||||
Keywords | OXIDOREDUCTASE / aldehyde dehydrogenase / NAD / lysine catabolism | ||||||
Function / homology | Function and homology information 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Tanner, J.J. | ||||||
Citation | Journal: Biochemistry / Year: 2015 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4zvw.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb4zvw.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 4zvw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4zvw_validation.pdf.gz | 469 KB | Display | wwPDB validaton report |
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Full document | 4zvw_full_validation.pdf.gz | 480.4 KB | Display | |
Data in XML | 4zvw_validation.xml.gz | 128.3 KB | Display | |
Data in CIF | 4zvw_validation.cif.gz | 177.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zv/4zvw ftp://data.pdbj.org/pub/pdb/validation_reports/zv/4zvw | HTTPS FTP |
-Related structure data
Related structure data | 4zukC 4zulC 4zvxC 4zvyC 2j6lS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: 1
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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.) Homo sapiens (human) / Gene: ALDH7A1, ATQ1 / Production host: Escherichia coli (E. coli) References: UniProt: P49419, L-aminoadipate-semialdehyde dehydrogenase, aldehyde dehydrogenase (NAD+), betaine-aldehyde dehydrogenase #2: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.29 Å3/Da / Density % sol: 46.26 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: The reservoir contained 0.2 M ammonium sulfate, 20% (w/v) polyethylene glycol (PEG) 3350, and 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: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å | |||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 26, 2013 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.4→159.64 Å / Num. obs: 153212 / % possible obs: 98.2 % / Redundancy: 3.7 % / Biso Wilson estimate: 28.9 Å2 / CC1/2: 0.967 / Rmerge(I) obs: 0.15 / Rpim(I) all: 0.092 / Net I/σ(I): 6.3 / Num. measured all: 559499 / Scaling rejects: 7 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2J6L Resolution: 2.4→159.636 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 2.04 / Phase error: 26.96 / 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: 95.45 Å2 / Biso mean: 37.2518 Å2 / Biso min: 4.09 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.4→159.636 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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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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