PDB-6o4d: Structure of ALDH7A1 mutant W175A complexed with L-pipecolic acid

ID or keywords:

Entry

Database: PDB / ID: 6o4d

Title

Structure of ALDH7A1 mutant W175A complexed with L-pipecolic acid

Components

(Alpha-aminoadipic semialdehyde ...) x 3

Keywords

OXIDOREDUCTASE / ALDEHYDE DEHYDROGENASE / NAD / LYSINE CATABOLISM

Function / homology

Function and homology information

L-aminoadipate-semialdehyde dehydrogenase activity / L-aminoadipate-semialdehyde dehydrogenase / Choline catabolism / choline catabolic process / Lysine catabolism / betaine-aldehyde dehydrogenase (NAD+) activity / betaine-aldehyde dehydrogenase / aldehyde metabolic process / glycine betaine biosynthetic process from choline / aldehyde dehydrogenase (NAD+) ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

FOURIER SYNTHESIS / Resolution: 1.88 Å

Authors

Tanner, J.J. / Korasick, D.A. / Laciak, A.R.

Funding support

United States, 1items

Citation

Journal: Febs J. / Year: 2020
Title: Structural and biochemical consequences of pyridoxine-dependent epilepsy mutations that target the aldehyde binding site of aldehyde dehydrogenase ALDH7A1.
Authors: Laciak, A.R. / Korasick, D.A. / Wyatt, J.W. / Gates, K.S. / Tanner, J.J.

History

Deposition	Feb 28, 2019	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jul 24, 2019	Provider: repository / Type: Initial release
Revision 1.1	Jan 1, 2020	Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2	Jan 15, 2020	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation.year / _citation_author.identifier_ORCID
Revision 1.3	Oct 11, 2023	Group: Data collection / Database references / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4	Nov 15, 2023	Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	6o4d.cif.gz	1.5 MB	Display	PDBx/mmCIF format
PDB format	pdb6o4d.ent.gz	1.2 MB	Display	PDB format
PDBx/mmJSON format	6o4d.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/o4/6o4d ftp://data.pdbj.org/pub/pdb/validation_reports/o4/6o4d	HTTPS FTP

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Related structure data

Related structure data	6o4bC 6o4cC 6o4eC 6o4fC 6o4gC 6o4hC 4zulS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	6o4i-1 4zul-1 6o4h-2 6o4i-2 6o4g-1 6o4g-2 6o4e-1 6o4e-2 6o4k-2 4zul-2 Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#127 - Jul 2010 Crystallins similarity (6) #89 - May 2007 Aconitase and Iron Regulatory Protein 1 similarity (6)

Deposited unit

A: Alpha-aminoadipic semialdehyde dehydrogenase

B: Alpha-aminoadipic semialdehyde dehydrogenase

C: Alpha-aminoadipic semialdehyde dehydrogenase

D: Alpha-aminoadipic semialdehyde dehydrogenase

E: Alpha-aminoadipic semialdehyde dehydrogenase

F: Alpha-aminoadipic semialdehyde dehydrogenase

G: Alpha-aminoadipic semialdehyde dehydrogenase

H: Alpha-aminoadipic semialdehyde dehydrogenase

hetero molecules

448 kDa, 8 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Alpha-aminoadipic semialdehyde dehydrogenase

B: Alpha-aminoadipic semialdehyde dehydrogenase

C: Alpha-aminoadipic semialdehyde dehydrogenase

D: Alpha-aminoadipic semialdehyde dehydrogenase

hetero molecules

defined by author
224 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

E: Alpha-aminoadipic semialdehyde dehydrogenase

F: Alpha-aminoadipic semialdehyde dehydrogenase

G: Alpha-aminoadipic semialdehyde dehydrogenase

H: Alpha-aminoadipic semialdehyde dehydrogenase

hetero molecules

defined by author
224 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	155.775, 161.975, 159.044
Angle α, β, γ (deg.)	90.00, 94.88, 90.00
Int Tables number	5
Space group name H-M	C121

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Alpha-aminoadipic semialdehyde ... , 3 types, 8 molecules ABGCDEFH

#1: Protein	Alpha-aminoadipic semialdehyde dehydrogenase / ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / ...ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / Betaine aldehyde dehydrogenase / Delta1-piperideine-6-carboxylate dehydrogenase / P6c dehydrogenase / Mass: 55521.238 Da / Num. of mol.: 1 / Mutation: W175A 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: Protein	Alpha-aminoadipic semialdehyde dehydrogenase / ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / ...ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / Betaine aldehyde dehydrogenase / Delta1-piperideine-6-carboxylate dehydrogenase / P6c dehydrogenase Mass: 55553.238 Da / Num. of mol.: 2 / Mutation: W175A 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
#3: Protein	Alpha-aminoadipic semialdehyde dehydrogenase / ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / ...ALDH7A1 / Alpha-AASA dehydrogenase / Aldehyde dehydrogenase family 7 member A1 / Antiquitin-1 / Betaine aldehyde dehydrogenase / Delta1-piperideine-6-carboxylate dehydrogenase / P6c dehydrogenase Mass: 55505.238 Da / Num. of mol.: 5 / Mutation: W175A 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

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Non-polymers , 7 types, 2078 molecules

#4: Chemical	ChemComp-6PC / PYRIDINE-2-CARBOXYLIC ACID / PICOLINIC ACID Mass: 123.109 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C₆H₅NO₂
#5: Chemical	ChemComp-PGE / TRIETHYLENE GLYCOL Mass: 150.173 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C₆H₁₄O₄
#6: Chemical	ChemComp-PEG / DI(HYDROXYETHYL)ETHER Mass: 106.120 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₄H₁₀O₃
#7: Chemical	ChemComp-1PE / PENTAETHYLENE GLYCOL / PEG400 Mass: 238.278 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₀H₂₂O₆ / Comment: precipitant*YM
#8: Chemical	ChemComp-PG4 / TETRAETHYLENE GLYCOL Mass: 194.226 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C₈H₁₈O₅ / Comment: precipitant*YM
#9: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂H₆O₂
#10: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 2055 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.25 Å³/Da / Density % sol: 45.36 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2 Details: 0.1 M MgCl2, 0.1 M Tris pH 7.2, 0.1 M sodium acetate trihydrate, 20% (w/v) PEG 4000

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

ALS

/ Beamline: 4.2.2 / Wavelength: 1 Å

Detector

Type: RDI CMOS_8M / Detector: CMOS / Date: Apr 3, 2017

Radiation

Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 1 Å / Relative weight: 1

Reflection

Resolution: 1.88→62.9 Å / Num. obs: 316551 / % possible obs: 99.6 % / Redundancy: 3.6 % / CC_1/2: 0.998 / R_merge(I) obs: 0.063 / R_pim(I) all: 0.039 / R_rim(I) all: 0.074 / Net I/σ(I): 14 / Num. measured all: 1137039 / Scaling rejects: 55

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. measured all	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	Net I/σ(I) obs	% possible all
1.88-1.91	3.2	0.59	50415	15697	0.733	0.393	0.712	1.8	99.8
10.3-62.9	3.6	0.022	6919	1914	0.999	0.014	0.026	37.5	95.7

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Processing

Software

Name	Version	Classification
PHENIX	(1.14_3260: ???)	refinement
Aimless	0.5.31	data scaling
PDB_EXTRACT	3.24	data extraction
XDS		data reduction
PHENIX		phasing

Refinement

Method to determine structure:

FOURIER SYNTHESIS
Starting model: 4zul

4zul

Resolution: 1.88→57.962 Å / SU ML: 0.22 / Cross valid method: THROUGHOUT / σ(F): 1.07 / Phase error: 22.83 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.2152	28834	4.83 %
R_work	0.1723	-	-
obs	0.1744	596754	94.69 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 1.88→57.962 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	30718	0	231	2055	33004

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	31618
X-RAY DIFFRACTION	f_angle_d	0.767	42846
X-RAY DIFFRACTION	f_dihedral_angle_d	14.783	18682
X-RAY DIFFRACTION	f_chiral_restr	0.05	4802
X-RAY DIFFRACTION	f_plane_restr	0.005	5541

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.88-1.9014	0.3313	845	0.2904	18284	X-RAY DIFFRACTION	90
1.9014-1.9237	0.3406	946	0.2755	18674	X-RAY DIFFRACTION	94
1.9237-1.9472	0.3103	947	0.2634	19541	X-RAY DIFFRACTION	98
1.9472-1.9718	0.3033	854	0.2573	19638	X-RAY DIFFRACTION	97
1.9718-1.9978	0.2981	982	0.2526	19173	X-RAY DIFFRACTION	96
1.9978-2.0252	0.3014	914	0.2421	19125	X-RAY DIFFRACTION	95
2.0252-2.0541	0.2744	996	0.2293	18777	X-RAY DIFFRACTION	94
2.0541-2.0848	0.2907	972	0.2316	18535	X-RAY DIFFRACTION	92
2.0848-2.1173	0.2637	1025	0.2147	18212	X-RAY DIFFRACTION	92
2.1173-2.1521	0.2535	958	0.2127	18191	X-RAY DIFFRACTION	91
2.1521-2.1892	0.2598	953	0.2056	17990	X-RAY DIFFRACTION	90
2.1892-2.229	0.2568	989	0.2051	18246	X-RAY DIFFRACTION	92
2.229-2.2718	0.2531	952	0.2029	18344	X-RAY DIFFRACTION	92
2.2718-2.3182	0.2519	931	0.1929	18755	X-RAY DIFFRACTION	94
2.3182-2.3686	0.2391	893	0.1853	18924	X-RAY DIFFRACTION	95
2.3686-2.4237	0.2292	970	0.1799	19158	X-RAY DIFFRACTION	96
2.4237-2.4843	0.2421	985	0.181	19241	X-RAY DIFFRACTION	96
2.4843-2.5515	0.2206	912	0.1733	19647	X-RAY DIFFRACTION	98
2.5515-2.6266	0.2285	1043	0.1737	19609	X-RAY DIFFRACTION	98
2.6266-2.7114	0.2223	907	0.1737	19626	X-RAY DIFFRACTION	98
2.7114-2.8083	0.2452	1077	0.1795	19619	X-RAY DIFFRACTION	98
2.8083-2.9207	0.2274	986	0.1753	19404	X-RAY DIFFRACTION	98
2.9207-3.0536	0.2211	958	0.1713	19374	X-RAY DIFFRACTION	96
3.0536-3.2146	0.2335	1078	0.175	19016	X-RAY DIFFRACTION	96
3.2146-3.416	0.2005	1009	0.16	18754	X-RAY DIFFRACTION	94
3.416-3.6797	0.1893	930	0.1519	18699	X-RAY DIFFRACTION	94
3.6797-4.0499	0.1718	897	0.1376	18730	X-RAY DIFFRACTION	93
4.0499-4.6357	0.1498	1098	0.1212	18558	X-RAY DIFFRACTION	93
4.6357-5.8397	0.1533	889	0.1309	19009	X-RAY DIFFRACTION	95
5.8397-57.99	0.1587	938	0.1382	19067	X-RAY DIFFRACTION	95

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	0.3205	0.1118	-0.0124	0.462	0.1716	0.5287	0.0289	-0.0878	0.0574	-0.0252	0.0608	-0.1567	-0.0615	0.127	-0.0805	0.1701	-0.0023	0.0016	0.1626	-0.0809	0.2462	57.1905	58.6067	34.3848
2	0.6981	-0.2619	0.0853	0.4807	0.0356	0.3449	0.0116	-0.1081	0.0606	0.0225	0.0013	0.0665	-0.0164	-0.0293	-0.0105	0.1677	-0.0225	0.0021	0.1925	-0.0862	0.1974	21.8429	58.1722	43.1952
3	0.8417	-0.1547	0.0523	0.2433	-0.0442	0.2128	0.0037	0.0725	-0.1446	-0.0733	-0.0275	0.0438	0.0107	-0.0393	0.0229	0.1835	-0.0056	-0.0289	0.1339	-0.0552	0.2147	45.3016	18.6198	23.3463
4	0.8083	0.1465	-0.0397	0.4944	-0.0929	0.325	0.0367	-0.2698	-0.164	0.1218	-0.0433	-0.051	0.0351	0.066	0.0044	0.1816	-0.0223	-0.026	0.2628	0.016	0.1766	36.0895	20.2611	58.4262
5	0.5191	0.3504	-0.0538	0.45	-0.0103	0.2362	-0.0328	0.0541	-0.0778	-0.043	0.0273	-0.0138	0.014	-0.044	0.0063	0.1856	-0.0219	0.0126	0.2536	-0.1222	0.2197	23.3435	98.4254	33.238
6	0.4302	-0.1271	-0.12	0.3356	-0.0436	0.3955	-0.0125	0.0133	-0.0434	0.027	0.007	-0.1027	0.0179	-0.0162	0.0122	0.1785	-0.0411	-0.005	0.1959	-0.0995	0.2674	58.3931	99.1865	43.207
7	0.3211	0.02	-0.0035	0.2824	-0.1296	0.4083	-0.0202	-0.0701	0.101	-0.0215	0.0057	0.0244	-0.0593	-0.0769	0.0128	0.1859	0.0183	-0.0111	0.1926	-0.0882	0.1891	35.5873	138.093	21.3463
8	0.5425	-0.0637	-0.1694	0.2636	0.0544	0.272	0.0063	-0.1429	0.0453	0.0549	0.0174	-0.0119	-0.0504	-0.0504	-0.0241	0.2077	-0.0053	0.009	0.2539	-0.0805	0.1709	43.6545	137.5513	56.7209

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	peptide and chain A
2	X-RAY DIFFRACTION	2	peptide and chain B
3	X-RAY DIFFRACTION	3	peptide and chain C
4	X-RAY DIFFRACTION	4	peptide and chain D
5	X-RAY DIFFRACTION	5	peptide and chain E
6	X-RAY DIFFRACTION	6	peptide and chain F
7	X-RAY DIFFRACTION	7	peptide and chain G
8	X-RAY DIFFRACTION	8	peptide and chain H

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