PDB-7mzy: Anaplastic lymphoma kinase (ALK) extracellular fragment of ligand...

ID or keywords:

Entry

Database: PDB / ID: 7mzy

Title

Anaplastic lymphoma kinase (ALK) extracellular fragment of ligand binding region 673-986

Components

ALK tyrosine kinase receptor

Keywords

TRANSFERASE / Anaplastic lymphoma kinase / Receptor tyrosine kinases / RTK / FAM150 / LTK / DE NOVO PROTEIN

Function / homology

Function and homology information

ASP-3026-resistant ALK mutants / NVP-TAE684-resistant ALK mutants / alectinib-resistant ALK mutants / brigatinib-resistant ALK mutants / ceritinib-resistant ALK mutants / crizotinib-resistant ALK mutants / lorlatinib-resistant ALK mutants / MDK and PTN in ALK signaling / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MAD / Resolution: 1.5 Å

Authors

Reshetnyak, A.V. / Sowaileh, M. / Miller, D.J. / Rossi, P. / Myasnikov, A.G. / Kalodimos, C.G.

Funding support

United States, 1items

Citation

Journal: Nature / Year: 2021
Title: Mechanism for the activation of the anaplastic lymphoma kinase receptor.
Authors: Andrey V Reshetnyak / Paolo Rossi / Alexander G Myasnikov / Munia Sowaileh / Jyotidarsini Mohanty / Amanda Nourse / Darcie J Miller / Irit Lax / Joseph Schlessinger / Charalampos G Kalodimos /

Abstract: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that regulates important functions in the central nervous system. The ALK gene is a hotspot for chromosomal translocation events ...

History

Deposition	May 24, 2021	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 24, 2021	Provider: repository / Type: Initial release
Revision 1.1	Dec 8, 2021	Group: Database references / Category: citation / citation_author Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2	Dec 15, 2021	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7mzy.cif.gz	280.8 KB	Display	PDBx/mmCIF format
PDB format	pdb7mzy.ent.gz	194.3 KB	Display	PDB format
PDBx/mmJSON format	7mzy.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7mzy_validation.pdf.gz	449 KB	Display	wwPDB validaton report
Full document	7mzy_full_validation.pdf.gz	454.7 KB	Display
Data in XML	7mzy_validation.xml.gz	27.4 KB	Display
Data in CIF	7mzy_validation.cif.gz	41.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/mz/7mzy ftp://data.pdbj.org/pub/pdb/validation_reports/mz/7mzy	HTTPS FTP

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Related structure data

Related structure data	24095C 7mzwC 7mzxC 7mzzC 7n00C C: citing same article (ref.)
Similar structure data	4hao-2 2an1-2 5fa9-d 3lok-d 4g9i-2 3c7j-d 4nwb-2 4l68-d 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	#70 - Oct 2005 Designer Proteins similarity (1) #182 - Feb 2015 Insulin receptor similarity (2) #159 - Mar 2013 Erythrocruorin similarity (3) #68 - Aug 2005 Neurotrophins similarity (2) #43 - Jul 2003 Src Tyrosine Kinase similarity (1) #60 - Dec 2004 Ubiquitin similarity (1)

Deposited unit

A: ALK tyrosine kinase receptor

B: ALK tyrosine kinase receptor

hetero molecules

64.7 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	70.289, 133.356, 62.909
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	18
Space group name H-M	P2₁2₁2
Space group name Hall	P22ab
Symmetry operation	#1: x,y,z #2: x+1/2,-y+1/2,-z #3: -x+1/2,y+1/2,-z #4: -x,-y,z

#1: Protein	ALK tyrosine kinase receptor / Anaplastic lymphoma kinase Mass: 32289.629 Da / Num. of mol.: 2 / Fragment: Ligand binding region, residues 673-986 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ALK / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) References: UniProt: Q9UM73, receptor protein-tyrosine kinase
#2: Chemical	ChemComp-ACT / ACETATE ION Mass: 59.044 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂H₃O₂
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 452 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	N

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.28 Å³/Da / Density % sol: 46.12 %
Crystal grow	Temperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 25.5 % PEG 4000, 15% glycerol, 0.17 M ammonium acetate and 0.085M sodium citrate pH 5.6

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Data collection

Diffraction

ID	Mean temperature (K)	Crystal-ID	Serial crystal experiment
1	100	1	N
2	100	1	N

Diffraction source

Source	Site	Beamline	ID	Wavelength	Wavelength (Å)
SYNCHROTRON	APS	22-ID	1	1.0, 0.97911, 0.97166
SYNCHROTRON	APS	22-ID	2		1

Detector

Type	ID	Detector	Date
DECTRIS PILATUS 2M	1	PIXEL	Jun 21, 2019
DECTRIS PILATUS 2M	2	PIXEL	Jul 8, 2019

Radiation

ID	Protocol	Monochromatic (M) / Laue (L)	Scattering type	Wavelength-ID
1	MAD	M	x-ray	1
2	MAD	M	x-ray	2

Radiation wavelength

ID	Wavelength (Å)	Relative weight
1	1	1
2	0.97911	1
3	0.97166	1

Reflection

Resolution: 1.5→50 Å / Num. obs: 95109 / % possible obs: 92.3 % / Observed criterion σ(I): 2 / Redundancy: 11.6 % / B_iso Wilson estimate: 12.95 Å² / CC_1/2: 0.985 / Net I/σ(I): 22.4

Reflection shell

Resolution: 1.5→1.53 Å / Redundancy: 7.6 % / Num. unique obs: 2895 / CC_1/2: 0.874 / % possible all: 61.6

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Processing

Software

Name	Version	Classification
PHENIX	1.19.1_4122	refinement
HKL-2000		data reduction
HKL-2000		data scaling
PHENIX		phasing

Refinement

Method to determine structure:

MAD / Resolution: 1.5→37.57 Å / SU ML: 0.1448 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 19.9713
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.1965	5211	6.76 %
R_work	0.1678	71912	-
obs	0.1698	77123	80.26 %

Solvent computation

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

Displacement parameters

B_iso mean: 22.25 Å²

Refinement step

Cycle: LAST / Resolution: 1.5→37.57 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	4353	0	8	453	4814

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0117	4520
X-RAY DIFFRACTION	f_angle_d	1.1542	6126
X-RAY DIFFRACTION	f_chiral_restr	0.1059	624
X-RAY DIFFRACTION	f_plane_restr	0.0084	832
X-RAY DIFFRACTION	f_dihedral_angle_d	6.483	657

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 (%)
1.5-1.51	0.3083	72	0.2962	941	X-RAY DIFFRACTION	32.21
1.51-1.53	0.3212	95	0.2775	1236	X-RAY DIFFRACTION	42.01
1.53-1.55	0.3152	101	0.2455	1397	X-RAY DIFFRACTION	47.21
1.55-1.57	0.2237	103	0.2211	1508	X-RAY DIFFRACTION	50.41
1.57-1.59	0.2666	112	0.2073	1590	X-RAY DIFFRACTION	54.8
1.59-1.61	0.2441	128	0.1973	1698	X-RAY DIFFRACTION	57.42
1.61-1.63	0.2262	128	0.1906	1840	X-RAY DIFFRACTION	62.24
1.63-1.66	0.1842	138	0.1875	1894	X-RAY DIFFRACTION	63.98
1.66-1.68	0.2441	152	0.1846	2011	X-RAY DIFFRACTION	68.08
1.68-1.71	0.2493	153	0.1789	2104	X-RAY DIFFRACTION	70.55
1.71-1.74	0.2246	155	0.1753	2129	X-RAY DIFFRACTION	73.09
1.74-1.77	0.1932	161	0.1827	2270	X-RAY DIFFRACTION	76.76
1.77-1.81	0.1976	163	0.1805	2256	X-RAY DIFFRACTION	76.21
1.81-1.84	0.2173	176	0.1745	2452	X-RAY DIFFRACTION	82.2
1.84-1.88	0.1959	200	0.1759	2689	X-RAY DIFFRACTION	90.76
1.88-1.93	0.2025	203	0.1808	2776	X-RAY DIFFRACTION	94.06
1.93-1.98	0.1989	207	0.1796	2854	X-RAY DIFFRACTION	95.54
1.98-2.03	0.1943	206	0.1657	2898	X-RAY DIFFRACTION	96.91
2.03-2.09	0.1929	212	0.1574	2904	X-RAY DIFFRACTION	97.77
2.09-2.16	0.1986	213	0.1635	2934	X-RAY DIFFRACTION	98.19
2.16-2.23	0.1994	214	0.1585	2919	X-RAY DIFFRACTION	97.91
2.23-2.32	0.1867	209	0.1601	2905	X-RAY DIFFRACTION	97.62
2.32-2.43	0.1867	214	0.1664	2948	X-RAY DIFFRACTION	97.83
2.43-2.56	0.2058	197	0.1593	2748	X-RAY DIFFRACTION	91.95
2.56-2.72	0.1821	202	0.1669	2874	X-RAY DIFFRACTION	94.91
2.72-2.93	0.2332	216	0.1634	2985	X-RAY DIFFRACTION	99.5
2.93-3.22	0.1788	221	0.1576	3033	X-RAY DIFFRACTION	99.69
3.22-3.69	0.1672	221	0.1534	3034	X-RAY DIFFRACTION	99.63
3.69-4.65	0.1592	220	0.1406	3040	X-RAY DIFFRACTION	98.61
4.65-37.57	0.2181	219	0.1924	3045	X-RAY DIFFRACTION	94.12

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	0.0124346911995	-0.00773793428187	0.0189874775824	0.0213002046668	-0.0200937115489	0.027115484552	0.0228590675875	-0.0258913728341	-0.0536865779407	0.0551376903801	0.0306385235663	-0.0324308029331	0.0733532303716	0.0281273037359	0.050514524412	0.145913224616	0.0343855633282	-0.123509551045	-0.0141107717964	0.124115576774	0.133079042093	16.7366813337	33.6423308291	52.7392037256
2	0.00429762013095	-0.000319555626172	0.005028142987	0.0274961340383	-0.00832834447886	0.00922757276844	0.0267943653881	-0.0178202351274	-0.0425318886872	0.0372829531799	0.00594098213591	-0.0287306961802	0.0313795543971	0.0117557942742	0.017121154706	0.290403196947	0.0290532255119	-0.114114847286	0.0856315313849	0.117851842986	0.154373594652	13.9934758153	36.3147103185	59.8485343854
3	0.0329416270756	-0.00371625918523	-0.0102691899999	0.023300340467	-0.00700655929373	0.0114243378668	0.0157004358627	0.0049314914624	-0.0817058876255	0.083544344566	-0.0252397857699	-0.148298216811	0.0361937585504	0.039035936868	-0.010802443155	0.12867017612	0.016444560007	-0.0629803569232	0.0800302151335	0.00432751754946	0.125002061315	18.9906089094	43.897698508	47.7570362792
4	0.00100934825381	-0.00128108859886	0.00045348780646	0.00256945467241	-0.00128552873929	0.00214378468735	0.0211767317394	0.0523709336447	-0.00706271062554	-0.044441089958	0.00122806295766	-0.00993217026146	-0.00263706525413	0.0221816057085	0.000640429346045	0.160623592417	0.0365250813779	-0.00874184112918	0.118035715726	-0.0171691543392	0.0543089740256	2.15640891598	54.5093571943	21.4267124798
5	0.0195806062147	-0.00390862464512	0.00291765098861	0.0015894566394	0.00110970608663	0.0203159402629	0.0138776703138	0.0215853479177	0.00578117016995	0.0349928668538	0.0132674376706	-0.0250324302083	0.00555571240704	-0.0120795996301	0.0114941902202	0.103412219655	0.0179058289148	-0.0759881833156	0.0510824627777	0.0324611184956	0.0535901003277	16.213898362	49.2876097438	55.7363264509
6	0.00219706526744	-0.0167012340573	0.00701113415032	0.104799298716	0.033587054715	0.00456001883927	0.0236202103033	0.031657852155	-0.00107001498461	0.0174312103166	0.0122679512902	-0.130986342507	-0.0133751244286	0.00795049052021	0.0065747529111	0.0578716666085	0.00128124469258	-0.0172237652618	0.0753581667474	0.00983374051373	0.0721099342346	12.7612194248	55.7534202841	43.2032858311
7	0.0100991166762	0.00572630923938	0.00201711554109	0.00292516326696	0.000594497896219	6.36851092476E-5	-0.00589835137954	-0.0152632536642	-0.00934587889958	0.0259556265946	0.0133455537141	-0.0353582069791	0.0151882430162	0.0376806623851	0.0161729676146	0.172008781198	0.0452767013569	-0.123046452284	0.14091506051	0.0171755509114	0.23662499858	28.054974783	41.7453151142	50.4418407414
8	0.00042864153584	0.000396066757381	0.00247454164609	0.00176055377705	0.0020644973715	0.0014104541729	0.00309005528734	0.0277517079123	-0.070007814861	-0.0251883534142	0.0163572738777	-0.0211886072067	0.0508473225757	-0.0166961889225	0.0105466702237	0.0844022878312	-0.0329112372024	-0.0493935504398	0.0498237431953	-0.0682912288404	0.274097824402	49.6381850982	37.4498828052	38.9917355226
9	0.0346787405211	0.00999534225854	-0.00342685402257	0.0453852459226	0.00602145325921	0.00117343511649	0.0320864834521	-0.0169681125766	-0.151266478271	-0.0244752995906	-0.0455122242253	-0.0166855325233	-0.0256757122777	-0.0507266304152	-0.0128887772006	0.0759490833454	-0.0145139696689	0.000404830220522	0.114297625256	-0.0225285201925	0.0829578540991	44.4503462872	48.7898490512	41.7896289862
10	0.0130286894333	0.0169881589308	-0.00222728130393	0.0257580824827	-0.000127053797039	0.0293104176173	0.0139382614538	0.010691651245	-0.123174799142	0.00683723720065	-0.0682080168761	-0.0276316857267	0.0083829856294	0.00435890595111	-0.0484949521718	0.101330597439	-0.014560614176	0.000293173623401	0.0823496779185	-0.0096066159969	0.0843694057197	51.4820926434	45.7250889932	42.9029742984
11	0.0320525412126	-0.00825804148008	-0.00945672942135	0.0298565624014	0.0191786284175	0.0251630825174	0.00714058499361	-0.0392560525873	-0.0866728066375	0.0777249550868	-0.0290914011241	-0.00542473571217	-0.0198158129531	-0.0381051943893	-0.0274436443623	0.128878830533	-0.0513151381392	-0.0109682801353	0.108596799359	0.00566783275164	0.0197638412527	57.4756860724	55.3891473546	57.2833775192
12	0.000808018038129	0.00123987893672	0.0027301462131	0.00534090648299	-0.00193110367568	0.00329865915149	0.0273470303438	-0.00212875648097	0.0233451488899	-0.00682442749823	-0.000873176281649	0.0169068314448	-0.0104129755419	-0.00348663277249	0.00583381468121	0.0784841199901	-0.000321898288277	-0.00744451154703	0.0828590039188	-0.00746276303715	0.0993078076836	49.2126372719	64.8273174198	43.0115140871
13	0.0220369387773	0.0194525169188	-0.00760810363355	0.0447322096715	-0.00985796311457	0.0134294828015	0.026205694512	-0.00797836998516	-0.0160288328231	0.0282713075555	-0.0152144768757	0.00170196901473	-0.00817157219513	-0.00475093042615	-0.00763021306897	0.062709169465	-0.0126043335079	-0.00621699907935	0.0739057700326	-0.0093367681736	0.072913406841	58.2700708366	57.6650736064	49.6267424145
14	0.00259031643712	0.000687160923894	0.00106515622316	0.00368533023032	-0.00149306560975	-4.13464183861E-5	0.0227248900317	0.00569643243857	-0.0525109817468	0.0201010966389	-0.00854143752967	0.024805013352	0.00127322423607	-0.0448766689035	-1.13129077302E-5	0.0929201231559	-0.00896415930851	-0.0129476398838	0.128580482417	-0.02154105015	0.118719388983	36.4494484795	49.7264515919	41.6606119021

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 677 through 704 )	A	A	677 - 704	1 - 28
2	2	chain 'A' and (resid 705 through 731 )	A	A	705 - 731	29 - 55
3	3	chain 'A' and (resid 732 through 787 )	A	A	732 - 787	56 - 109
4	4	chain 'A' and (resid 788 through 817 )	A	A	788 - 817	110 - 139
5	5	chain 'A' and (resid 818 through 833 )	A	A	818 - 833	140 - 155
6	6	chain 'A' and (resid 834 through 963 )	A	A	834 - 963	156 - 285
7	7	chain 'A' and (resid 964 through 985 )	A	A	964 - 985	286 - 307
8	8	chain 'B' and (resid 680 through 717 )	B	D	680 - 717	1 - 38
9	9	chain 'B' and (resid 718 through 765 )	B	D	718 - 765	39 - 86
10	10	chain 'B' and (resid 766 through 787 )	B	D	766 - 787	87 - 108
11	11	chain 'B' and (resid 788 through 851 )	B	D	788 - 851	109 - 172
12	12	chain 'B' and (resid 857 through 876 )	B	D	857 - 876	173 - 192
13	13	chain 'B' and (resid 877 through 963 )	B	D	877 - 963	193 - 279
14	14	chain 'B' and (resid 964 through 986 )	B	D	964 - 986	280 - 302

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