PDB-8v9m: Human Ornithine Aminotransferase cocrystallized with its inhibito...

ID or keywords:

Entry

Database: PDB / ID: 8v9m

Title

Human Ornithine Aminotransferase cocrystallized with its inhibitor, (R)-3-amino-5,5-difluorocyclohex-1-ene-1-carboxylic acid.

Components

Ornithine aminotransferase, mitochondrial

Keywords

TRANSFERASE / PLP / Ornithine Aminotransferase / Mechanism-based Inactivator / heptocellular carcinoma

Function / homology

Function and homology information

L-arginine catabolic process to proline via ornithine / ornithine aminotransferase activity / ornithine aminotransferase / L-arginine catabolic process to L-glutamate / L-proline biosynthetic process / Glutamate and glutamine metabolism / visual perception / pyridoxal phosphate binding / mitochondrial matrix / mitochondrion ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.61 Å

Authors

Vargas, A.L. / Devitt, A. / Kaley, N. / Silverman, R. / Liu, D.

Funding support

United States, 1items

Citation

Journal: Acs Chem.Biol. / Year: 2024
Title: Design, Synthesis, and Mechanistic Studies of ( R )-3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase.
Authors: Devitt, A.N. / Vargas, A.L. / Zhu, W. / Des Soye, B.J. / Butun, F.A. / Alt, T. / Kaley, N. / Ferreira, G.M. / Moran, G.R. / Kelleher, N.L. / Liu, D. / Silverman, R.B.

History

Deposition	Dec 8, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	May 8, 2024	Provider: repository / Type: Initial release
Revision 1.1	May 29, 2024	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8v9m.cif.gz	607.3 KB	Display	PDBx/mmCIF format
PDB format	pdb8v9m.ent.gz	414.9 KB	Display	PDB format
PDBx/mmJSON format	8v9m.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8v9m_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	8v9m_full_validation.pdf.gz	1.4 MB	Display
Data in XML	8v9m_validation.xml.gz	57.4 KB	Display
Data in CIF	8v9m_validation.cif.gz	86.3 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/v9/8v9m ftp://data.pdbj.org/pub/pdb/validation_reports/v9/8v9m	HTTPS FTP

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Related structure data

Similar structure data	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

Deposited unit

A: Ornithine aminotransferase, mitochondrial

B: Ornithine aminotransferase, mitochondrial

C: Ornithine aminotransferase, mitochondrial

hetero molecules

136 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Ornithine aminotransferase, mitochondrial

hetero molecules

A: Ornithine aminotransferase, mitochondrial

hetero molecules

defined by author&software
90.7 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Ornithine aminotransferase, mitochondrial

hetero molecules

C: Ornithine aminotransferase, mitochondrial

hetero molecules

defined by author&software
90.8 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	115.334, 115.334, 186.292
Angle α, β, γ (deg.)	90.000, 90.000, 120.000
Int Tables number	154
Space group name H-M	P3₂21
Space group name Hall	P3₂2"
Symmetry operation	#1: x,y,z #2: -y,x-y,z+2/3 #3: -x+y,-x,z+1/3 #4: x-y,-y,-z+1/3 #5: -x,-x+y,-z+2/3 #6: y,x,-z

Components on special symmetry positions

ID	Model	Components
1	1	A-701- HOH
2	1	A-940- HOH
3	1	C-692- HOH
4	1	C-968- HOH

#1: Protein	Ornithine aminotransferase, mitochondrial / Ornithine delta-aminotransferase / Ornithine--oxo-acid aminotransferase Mass: 44860.320 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OAT / Production host: Escherichia coli (E. coli) / References: UniProt: P04181, ornithine aminotransferase
#2: Chemical	ChemComp-YR5 / 3-fluoro-5-[({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino]benzoic acid Mass: 386.269 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₁₅H₁₆FN₂O₇P / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₃H₈O₃
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 1132 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.68 Å³/Da / Density % sol: 54.06 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 10% PEG 6000, 100 mM NaCl, 20% glycerol, 100 mM tricine, pH 7.8

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.1272 Å
Detector	Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Dec 14, 2022
Radiation	Monochromator: M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.1272 Å / Relative weight: 1
Reflection	Resolution: 1.61→99.882 Å / Num. obs: 186618 / % possible obs: 99.96 % / Redundancy: 13.5 % / B_iso Wilson estimate: 23.46 Å² / CC_1/2: 0.998 / Net I/σ(I): 10.7
Reflection shell	Resolution: 1.61→1.63 Å / Redundancy: 13.3 % / Num. unique obs: 9233 / CC_1/2: 0.354 / % possible all: 100

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Processing

Software

Name	Version	Classification
PHENIX	1.20.1_4487	refinement
autoPROC		data reduction
autoPROC		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.61→44.01 Å / SU ML: 0.203 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.2829
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.193	9222	4.94 %
R_work	0.1642	177366	-
obs	0.1656	186588	99.97 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL

Displacement parameters

B_iso mean: 34.13 Å²

Refinement step

Cycle: LAST / Resolution: 1.61→44.01 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	9471	0	102	1132	10705

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0151	9830
X-RAY DIFFRACTION	f_angle_d	1.3403	13363
X-RAY DIFFRACTION	f_chiral_restr	0.0855	1469
X-RAY DIFFRACTION	f_plane_restr	0.0112	1720
X-RAY DIFFRACTION	f_dihedral_angle_d	6.3109	1380

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 (%)
1.61-1.62	0.3196	330	0.2982	5854	X-RAY DIFFRACTION	99.94
1.62-1.64	0.3018	279	0.291	5822	X-RAY DIFFRACTION	99.98
1.64-1.66	0.3093	333	0.27	5853	X-RAY DIFFRACTION	100
1.66-1.68	0.3067	287	0.2693	5861	X-RAY DIFFRACTION	100
1.68-1.71	0.2811	260	0.2579	5921	X-RAY DIFFRACTION	100
1.71-1.73	0.3088	313	0.2727	5829	X-RAY DIFFRACTION	100
1.73-1.75	0.2716	343	0.2607	5853	X-RAY DIFFRACTION	100
1.75-1.78	0.2615	336	0.2426	5825	X-RAY DIFFRACTION	100
1.78-1.81	0.261	330	0.2344	5872	X-RAY DIFFRACTION	100
1.81-1.84	0.2648	308	0.2182	5854	X-RAY DIFFRACTION	100
1.84-1.87	0.2188	297	0.1966	5855	X-RAY DIFFRACTION	100
1.87-1.9	0.2339	294	0.1867	5901	X-RAY DIFFRACTION	100
1.9-1.94	0.2361	342	0.1797	5872	X-RAY DIFFRACTION	100
1.94-1.98	0.2112	299	0.1776	5886	X-RAY DIFFRACTION	100
1.98-2.02	0.224	288	0.1716	5902	X-RAY DIFFRACTION	100
2.02-2.07	0.1984	332	0.1728	5839	X-RAY DIFFRACTION	100
2.07-2.12	0.2167	270	0.1704	5920	X-RAY DIFFRACTION	99.87
2.12-2.18	0.2007	281	0.1695	5968	X-RAY DIFFRACTION	100
2.18-2.24	0.2066	283	0.164	5884	X-RAY DIFFRACTION	100
2.24-2.32	0.1923	286	0.1576	5928	X-RAY DIFFRACTION	100
2.32-2.4	0.1951	311	0.1597	5897	X-RAY DIFFRACTION	99.98
2.4-2.49	0.1932	282	0.158	5946	X-RAY DIFFRACTION	100
2.49-2.61	0.1966	321	0.1607	5920	X-RAY DIFFRACTION	100
2.61-2.75	0.1811	284	0.1593	5977	X-RAY DIFFRACTION	100
2.75-2.92	0.1958	354	0.1639	5857	X-RAY DIFFRACTION	100
2.92-3.14	0.19	311	0.1588	5970	X-RAY DIFFRACTION	100
3.14-3.46	0.1691	328	0.1522	5972	X-RAY DIFFRACTION	100
3.46-3.96	0.1533	286	0.137	6017	X-RAY DIFFRACTION	99.68
3.96-4.98	0.1585	302	0.1273	6069	X-RAY DIFFRACTION	99.89
4.99-44.01	0.1633	352	0.1473	6242	X-RAY DIFFRACTION	99.82

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	0.799060009723	-0.284867256398	-0.491761889014	0.537863345293	0.233168740704	0.772748047025	0.158893965965	-0.0869580032373	0.359613960201	-0.114676043626	0.066121403001	-0.27193502158	-0.218526524519	0.181160118932	-0.163397488385	0.199706271716	-0.0145230795665	0.10484662908	0.225367615907	-0.0454790649798	0.375695234455	-0.70090762257	-17.1969873721	-7.0868165368
2	5.26441623159	0.114406301074	-1.35977726863	0.945204405611	0.962990673851	1.52542192212	0.121942663453	-0.305807554001	-0.183962145799	0.171026609886	0.16939168617	-0.424617776503	0.18595046043	0.732904630432	-0.151387319367	0.188353460142	0.0382567834955	-0.0077211095362	0.50293031611	-0.222523190714	0.631438448279	21.7082249831	-26.4100304156	-3.09705068796
3	0.86880585128	-0.291845091154	0.347818523758	0.18674140466	0.0304250810309	0.383094389365	0.115307626429	-0.171143340399	0.144162659034	-0.000839827465738	0.229886983822	-0.280622007873	-0.120851367009	0.47092414691	0.0616192466138	0.0941674729904	-0.0495649969012	0.0729387327647	0.743298969418	-0.375668119228	0.778885174466	22.0161366483	-19.897935695	3.88041667139
4	2.11730614254	-0.688478117112	0.282954292694	0.996665968307	-0.487316052082	0.909680053914	0.0142306524853	-0.0746047755471	0.327471437753	0.134637658612	0.0607491432355	0.0638093785053	-0.333750988182	-0.598736644944	-0.0350180167893	0.303601815058	0.142990580412	0.0582391104958	0.473154388108	0.0218901903752	0.249907599991	-11.1875539224	-45.8485660805	57.3844331627
5	0.729472478975	-0.0837932736087	-0.0506588500341	0.616468843299	-0.118219246236	1.01410530417	0.0573160847276	0.162163945748	-0.000397740765242	-0.0790526606093	-0.0115511267493	0.0636353544446	-0.0576422078032	-0.329994009891	-0.0482099543647	0.165221637904	0.00601678434634	-0.0214417410037	0.321877302193	-0.00123098903152	0.135920521857	2.71087861177	-60.2953413297	38.2533529667
6	1.57521794471	-1.20763358271	-0.188026140683	2.31225657829	0.199952929855	2.26613981015	0.121532028076	0.101107598037	0.489517124392	-0.0485764731018	0.0574062282056	-0.0882040205673	-0.715859608707	-0.401120233372	-0.115284672544	0.510766649475	0.232949192839	0.0756365880977	0.397613359167	0.0621889580488	0.360914560463	-6.33396264707	-32.9505391944	42.6682265622
7	4.86942375441	-0.65152547233	-0.366779125547	1.01951264228	1.39849660987	2.230879109	-0.0179133300246	0.044206092634	-0.299130210717	-0.101848494189	-0.020850278053	-0.287722931536	0.442897956541	0.740662480639	-0.0331894927057	0.366206218999	0.185332578767	0.0836247398218	0.565192824212	0.0131279190388	0.283564117312	16.6067563545	-68.1763180722	-20.8796731094
8	2.09315562681	-0.824781269803	-0.710081734976	3.78969809401	2.07119639057	2.40225258717	0.112254415938	0.468431299014	-0.248809046605	-0.113971815785	0.036779199587	-0.405018483822	0.187296487486	0.356921187751	-0.107227842332	0.319727495319	0.207530838414	-0.0198556087691	0.443770632603	-0.0650295572925	0.353136118369	21.7221606035	-72.8944677517	-5.22848057522
9	2.30011772317	-0.408831608092	0.350290269989	1.22884387833	0.372373039242	0.445881552688	0.105502144348	-0.0745219958093	-0.145951780541	0.138945532987	-0.0071454674733	-0.0163047764925	0.440637842774	0.137604661722	-0.0922000209928	0.418758983698	0.0839135303751	-0.0147265756179	0.212800501553	0.0257340162651	0.161704722326	-3.57104568988	-77.1655664339	1.98247257663
10	0.0998202090158	0.224669540915	0.243672513141	1.10729731553	0.494751496786	1.88423903347	-0.00144907963102	0.0129054664799	0.0598767856701	0.0501727692489	-0.0213610509336	0.0305709277794	0.0799422794041	-0.00350866034429	0.0265510286814	0.169020661188	0.0482173613798	0.0130493222524	0.189641874718	-0.0118236112868	0.172936816703	-7.66131806449	-50.9136751311	-2.49039380309
11	1.20000154683	0.38721936356	0.550194494923	1.19887104274	0.338876194425	1.32475709921	0.0208590763013	-0.126446993508	-0.0442676712804	0.179787015653	0.00085318594477	-0.025851699178	0.24533523416	0.0360392203739	-0.0340714003231	0.253836497869	0.0624418219967	0.0209157395129	0.201972465575	0.0123764694929	0.115219044436	-4.98008574042	-64.7491582885	6.07017339391
12	5.40636693521	1.82288805017	-0.330856158241	7.10764698475	-0.661039610816	3.04375263776	0.0742670115143	0.175717003489	0.530844555631	-0.25426189801	0.0568580041385	-0.339570443612	-0.0802292609553	0.410400253496	-0.129253841705	0.196761630443	0.116867843627	0.0142235181333	0.347593140468	-0.0175280751941	0.299919452696	20.171588595	-53.8645311201	5.13495727278
13	3.25602037452	1.21760564132	-1.97037535032	1.63488481793	0.0461180635524	3.04181875383	0.161097560073	0.284741921502	0.142028627351	-0.0439877377623	-0.0146503209464	-0.353274222777	0.0580102749401	0.397919175348	-0.1419157526	0.232756351286	0.155002764931	0.00591682013532	0.464237592526	-0.00346795549534	0.350374441916	23.549378557	-60.3359126582	-0.964119053824

Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

ID	Refine TLS-ID	Selection details	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	chain 'A' and (resid 36 through 344 )	A	A	36 - 344	1 - 309
2	2	chain 'A' and (resid 345 through 389 )	A	A	345 - 389	310 - 354
3	3	chain 'A' and (resid 390 through 439 )	A	A	390 - 439	355 - 404
4	4	chain 'B' and (resid 36 through 105 )	B	D	36 - 105	1 - 70
5	5	chain 'B' and (resid 106 through 344 )	B	D	106 - 344	71 - 309
6	6	chain 'B' and (resid 345 through 439 )	B	D	345 - 439	310 - 404
7	7	chain 'C' and (resid 36 through 61 )	C	H	36 - 61	1 - 26
8	8	chain 'C' and (resid 62 through 82 )	C	H	62 - 82	27 - 47
9	9	chain 'C' and (resid 83 through 141 )	C	H	83 - 141	48 - 106
10	10	chain 'C' and (resid 142 through 244 )	C	H	142 - 244	107 - 209
11	11	chain 'C' and (resid 245 through 344 )	C	H	245 - 344	210 - 309
12	12	chain 'C' and (resid 345 through 389 )	C	H	345 - 389	310 - 354
13	13	chain 'C' and (resid 390 through 439 )	C	H	390 - 439	355 - 404

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