PDB-7rci: Crystal Structure of a PMS2 VUS with Substrate

ID or keywords:

Entry

Database: PDB / ID: 7rci

Title

Crystal Structure of a PMS2 VUS with Substrate

Components

Mismatch repair endonuclease PMS2

Keywords

HYDROLASE / Mismatch Repair / Variant of Uncertain Significance / ATPase Domain / DNA Repair Enzyme

Function / homology

Function and homology information

single base insertion or deletion binding / Defective Mismatch Repair Associated With MLH1 / Defective Mismatch Repair Associated With PMS2 / MutLalpha complex / somatic recombination of immunoglobulin gene segments / positive regulation of isotype switching to IgA isotypes / positive regulation of isotype switching to IgG isotypes / Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) / Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) / ATP-dependent DNA damage sensor activity ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.12 Å

Authors

D'Arcy, B.M. / Prakash, A.

Citation

Journal: Mol Genet Genomic Med / Year: 2022
Title: PMS2 variant results in loss of ATPase activity without compromising mismatch repair.
Authors: D'Arcy, B.M. / Arrington, J. / Weisman, J. / McClellan, S.B. / Yang, Z. / Deivanayagam, C. / Blount, J. / Prakash, A.

History

Deposition	Jul 7, 2021	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Mar 2, 2022	Provider: repository / Type: Initial release
Revision 1.1	Nov 30, 2022	Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2	Oct 25, 2023	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7rci.cif.gz	304.9 KB	Display	PDBx/mmCIF format
PDB format	pdb7rci.ent.gz	204.8 KB	Display	PDB format
PDBx/mmJSON format	7rci.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7rci_validation.pdf.gz	1.7 MB	Display	wwPDB validaton report
Full document	7rci_full_validation.pdf.gz	1.7 MB	Display
Data in XML	7rci_validation.xml.gz	26.3 KB	Display
Data in CIF	7rci_validation.cif.gz	36.7 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/rc/7rci ftp://data.pdbj.org/pub/pdb/validation_reports/rc/7rci	HTTPS FTP

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Related structure data

Related structure data	7rcbC 7rckC 1h7sS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7rcb-d 1h7u-d 7rck-d 1h7s-d 3k2q-2 2rus-d 4nwb-2 3ivp-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	#150 - Jun 2012 Sliding Clamps similarity (2) #31 - Jul 2002 p53 Tumor Suppressor similarity (1) #122 - Feb 2010 Enhanceosome similarity (1) #213 - Sep 2017 Sirtuins similarity (1) #240 - Dec 2019 Hypoxia-Inducible Factors similarity (1) #221 - May 2018 Human Papillomavirus and Vaccines similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1)

Deposited unit

A: Mismatch repair endonuclease PMS2

B: Mismatch repair endonuclease PMS2

hetero molecules

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

1

Idetical with deposited unit
defined by author

Unit cell

Length a, b, c (Å)	75.059, 75.551, 135.663
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁
Space group name Hall	P2ac2ab
Symmetry operation	#1: x,y,z #2: x+1/2,-y+1/2,-z #3: -x,y+1/2,-z+1/2 #4: -x+1/2,-y,z+1/2

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
d_1	ens_1	(chain "A" and (resid 33 through 58 or (resid 59...
d_2	ens_1	(chain "B" and (resid 33 through 145 or (resid 146...

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Beg label comp-ID	End label comp-ID	Label asym-ID	Label seq-ID
d_1	1	ens_1	LEU	THR	A	4 - 55
d_1	2	ens_1	GLU	CYS	A	69 - 291
d_1	3	ens_1	LEU	ASP	A	298 - 317
d_2	1	ens_1	LEU	ASP	B	1 - 295

NCS oper: (Code: givenMatrix: (-0.0113046330959, 0.99950624427, -0.0293167688467), (0.999094152158, 0.0100873741816, -0.0413415046489), (-0.041025362827, -0.0297575628566, -0.998714877759)Vector: -16. ...

#1: Protein	Mismatch repair endonuclease PMS2 / DNA mismatch repair protein PMS2 / PMS1 protein homolog 2 Mass: 40486.207 Da / Num. of mol.: 2 / Mutation: N335S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PMS2, PMSL2 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): Rosetta2 (DE3 pLysS) References: UniProt: P54278, Hydrolases; Acting on ester bonds
#2: Chemical	ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE Mass: 507.181 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₀H₁₆N₅O₁₃P₃ / Feature type: SUBJECT OF INVESTIGATION / Comment: ATP, energy-carrying molecule*YM
#3: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 262 / 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: 2.38 Å³/Da / Density % sol: 48.22 %
Crystal grow	Temperature: 289.15 K / Method: vapor diffusion, hanging drop / pH: 5.8 Details: 1:1 7.5 mg/mL protein with 8% v/v Tacsimate, pH 5.8, 25% w/v PEG3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.03317 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 5, 2021
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.03317 Å / Relative weight: 1
Reflection	Resolution: 2.12→50.47 Å / Num. obs: 44441 / % possible obs: 99.79 % / Redundancy: 6.5 % / CC_1/2: 0.996 / CC star: 0.999 / R_merge(I) obs: 0.1012 / R_pim(I) all: 0.04359 / R_rim(I) all: 0.1105 / Χ²: 1 / Net I/σ(I): 8.63
Reflection shell	Resolution: 2.12→2.196 Å / Redundancy: 6.5 % / R_merge(I) obs: 0.7502 / Mean I/σ(I) obs: 1.73 / Num. unique obs: 4365 / CC_1/2: 0.776 / CC star: 0.935 / R_pim(I) all: 0.3151 / R_rim(I) all: 0.815 / Χ²: 1 / % possible all: 99.77

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Processing

Software

Name	Version	Classification
SAINT		data reduction
SADABS		data scaling
PHASER		phasing
PHENIX	V1.19	refinement
PDB_EXTRACT		data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB entry 1H7S

1h7s

Resolution: 2.12→50.47 Å / Cross valid method: FREE R-VALUE / σ(F): 19.48 / Phase error: 31.2464
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2481	4344	9.78 %
R_work	0.2225	40089	-
obs	0.2286	44433	99.8 %

Solvent computation

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

Displacement parameters

B_iso mean: 50.44 Å²

Refinement step

Cycle: LAST / Resolution: 2.12→50.47 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	4539	0	64	262	4865

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0024	4679
X-RAY DIFFRACTION	f_angle_d	0.4578	6373
X-RAY DIFFRACTION	f_chiral_restr	0.041	756
X-RAY DIFFRACTION	f_plane_restr	0.0035	818
X-RAY DIFFRACTION	f_dihedral_angle_d	13.0571	1632

Refine LS restraints NCS

Type: Torsion NCS / Rms dev position: 0.751874565683 Å

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 (%)
2.12-2.16	0.3544	235	0.3703	1973	X-RAY DIFFRACTION	89.15
2.16-2.2	0.3764	222	0.3486	1931	X-RAY DIFFRACTION	89.48
2.2-2.24	0.382	209	0.3432	1979	X-RAY DIFFRACTION	90.28
2.24-2.28	0.3772	243	0.3366	1969	X-RAY DIFFRACTION	88.97
2.28-2.33	0.3472	215	0.3329	1965	X-RAY DIFFRACTION	90.05
2.33-2.39	0.3189	202	0.3206	2004	X-RAY DIFFRACTION	90.72
2.39-2.45	0.4146	197	0.3144	1996	X-RAY DIFFRACTION	90.73
2.45-2.51	0.3262	183	0.3071	2019	X-RAY DIFFRACTION	91.27
2.51-2.59	0.3243	228	0.3077	1966	X-RAY DIFFRACTION	89.32
2.59-2.67	0.3593	199	0.3042	2003	X-RAY DIFFRACTION	90.84
2.67-2.77	0.3341	200	0.2988	2007	X-RAY DIFFRACTION	90.94
2.77-2.88	0.2795	220	0.281	2006	X-RAY DIFFRACTION	90.04
2.88-3.01	0.293	223	0.2568	1978	X-RAY DIFFRACTION	89.75
3.01-3.17	0.2713	239	0.249	1987	X-RAY DIFFRACTION	89.26
3.17-3.36	0.249	227	0.232	1989	X-RAY DIFFRACTION	89.59
3.37-3.62	0.216	235	0.2091	2000	X-RAY DIFFRACTION	89.41
3.62-3.99	0.2333	206	0.1816	2052	X-RAY DIFFRACTION	90.6
3.99-4.57	0.1861	206	0.1611	2038	X-RAY DIFFRACTION	90.7
4.57-5.75	0.1874	198	0.1668	2103	X-RAY DIFFRACTION	91.36
5.75-50.47	0.1874	222	0.1744	2159	X-RAY DIFFRACTION	89.88

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	3.6107255968	2.08651797725	-0.631579048136	4.51786371356	0.380173563026	2.38833899058	-0.0280870116096	0.103132948855	-0.340457821092	0.187511938023	0.0729516685787	-0.451996008796	-0.164830539952	0.140464689482	-0.0533103905135	0.321180581768	0.0199977608435	-0.0294170604576	0.188781808526	0.0201042636281	0.285773519693	3.959	9.319	-38.853
2	7.96679187051	2.10566893009	-2.46955790038	1.99036497349	2.23183361835	1.59558682202	0.720008420242	-0.25301965845	2.28702886757	0.809104480283	0.358548368578	3.65517059608	0.0837974503755	0.212591885645	-0.187455854659	0.909157813299	0.0557122609204	0.0698428519793	0.395959496213	0.203360607085	1.4347406632	2.977	13.012	-24.723
3	4.55663772289	-2.527611644	0.791425295933	5.60058215084	0.331544733783	3.85636187977	-0.100782096513	0.234999601049	-0.144966147779	-0.194232065256	-0.197750550174	-0.44732198659	-0.0272075193096	0.355879955324	0.302862598875	0.266543027931	-0.0636342924936	0.00744095978997	0.257716271732	0.0275872527159	0.245789106344	14.293	6.82	-42.424
4	1.18152670176	-1.12134145346	0.645556490293	2.67989281959	-0.383325447166	1.21154685592	-0.0259018920454	0.00237252325895	-0.276133504631	0.14070839226	0.0112484008481	0.28690878082	0.217694618849	-0.0302424441473	-0.00440149036282	0.467954176637	-0.0345836933154	0.0305473755606	0.214150266511	0.00480631420777	0.256195237855	-5.323	3.658	-39.137
5	3.5931409035	-0.601696557865	-0.815369068795	3.52311518495	1.60724073462	3.58161007683	-0.0109710659775	-0.257773102336	0.20684092294	0.316160901829	-0.106457687418	0.34992483176	0.229663755944	-0.219069472658	0.046388081715	0.389505188746	0.00318693545213	0.0608897939482	0.230416237215	0.0232546967392	0.27805139712	-20.631	22.657	-27.948
6	2.35126699574	0.739178079349	-0.381350101617	3.0708210125	0.587922147635	3.12481666527	0.187193137488	-0.340203936176	0.0696330244196	0.585432124699	-0.38909598576	0.391744430939	0.416347290183	-0.0995798923292	0.210060781472	0.633866048626	-0.0587855942623	0.116633807701	0.337716915947	-0.0352369720373	0.28712566772	-20.216	21.484	-21.709
7	5.70041982209	-0.341274610353	2.55482102777	2.12285177188	1.74488602447	3.71700648941	-0.0958588320556	0.264349189198	0.311881524481	-0.263153216656	0.230207667191	-0.252212633969	0.205502305608	0.00113869543213	-0.0577533737833	0.453554658399	-0.0470419638034	0.0332243081773	0.273319714825	0.0547965269664	0.21478598868	-6.37	20.197	-61.709
8	5.72419468693	-1.48909387316	0.230843483408	1.55876913717	-0.21560520883	1.52924397232	-0.13132896851	-0.292386853097	0.752910914746	-0.226635900093	0.178373494909	-0.0239348239573	-0.171779897678	0.296738179845	-0.0242118360924	0.70966997452	-0.0435941455164	-0.109062550126	0.289395054674	-0.030757245347	0.357047767556	-7.884	33.885	-60.488
9	2.03155459803	-0.191842478101	0.113795557071	0.495087123268	-0.719874202219	0.872335160074	-0.0277219433774	0.387495550873	-0.405293581739	-0.432388785637	0.120280317466	0.117163804679	0.150927687461	0.0282087448747	-0.0332015412491	0.511742614341	0.00367155940061	-0.0279532593763	0.351857990234	-0.0412241367779	0.315066565152	-15.013	15.281	-66.575
10	2.63526655242	-0.285877128579	-1.21787407609	0.638484981724	0.620286799236	2.03977475352	-0.377477688851	-0.122924538762	-0.498070411187	-0.0638688033411	0.168128792879	-0.00194535752315	0.238307132677	0.0876325743296	0.219291006292	0.504997898012	-0.0111623151419	0.0493151283121	0.254749033344	0.0278805764957	0.340986263047	-2.516	5.151	-56.591
11	0.524397846682	-0.084909026446	0.750414193567	0.885159197832	0.174950561998	1.32794635905	-0.893186264421	1.05873617961	-0.40129887066	0.0259687465638	-0.276495141193	-0.294698458435	0.371575733017	-0.422466620498	-0.296268204022	0.796119329902	-0.272227730465	0.551172897342	0.697870315473	-0.394487178261	0.451946369973	14.639	-2.038	-81.693
12	5.66914778283	2.09821325368	-1.47743998541	3.68397623433	-1.01192322217	1.85257633355	-0.189572199971	0.0625332388153	-0.807070672828	-0.592514736732	-0.504725764742	0.279370817998	0.462537463339	-0.0239293422605	0.46974725303	0.643868004467	-0.0505827839949	0.081609743401	0.372734988535	-0.0610582313893	0.406361320473	-0.267	-1.018	-70.902
13	0.122243211608	0.354116842611	-0.0943917130671	1.26480746537	-1.51621053284	3.51915446879	-0.530310611757	0.642778831375	-0.861712198946	-0.420831410398	0.262960169453	-0.707298101926	-0.160372194043	-0.893272245954	0.246548299291	0.793131183254	-0.422992164665	0.166244765823	0.748488067253	-0.337061660459	0.659682100747	-0.399	-8.695	-76.582
14	3.70857512621	-1.87082914538	0.539162854752	4.3309695069	1.06087818006	8.25668211537	-1.04048197114	1.30176690534	0.366171236824	-0.731286980946	0.174186573116	-0.21353510592	-0.277281991524	0.344044531993	0.749740744843	0.725286950227	-0.131081097058	-0.0275444015528	0.804355068134	0.0508715923126	0.284765045097	9.299	7.455	-78.178
15	2.12449807906	0.803606921244	0.629638252281	0.790793664119	1.49844051452	3.39764250828	-0.806151758912	0.677070733872	-0.456248649642	-0.130198331212	0.0877434407664	-0.00774262681705	0.608178378808	-0.486863966744	0.17722441048	0.875933227057	-0.272866120215	0.318544234466	0.706529141518	-0.247160488916	0.481402216341	10.464	-5.757	-79.855

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	( CHAIN A AND RESID 30:84 )	A	30 - 84
2	X-RAY DIFFRACTION	2	( CHAIN A AND RESID 85:109 )	A	85 - 109
3	X-RAY DIFFRACTION	3	( CHAIN A AND RESID 110:153 )	A	110 - 153
4	X-RAY DIFFRACTION	4	( CHAIN A AND RESID 154:222 )	A	154 - 222
5	X-RAY DIFFRACTION	5	( CHAIN A AND RESID 223:299 )	A	223 - 299
6	X-RAY DIFFRACTION	6	( CHAIN A AND RESID 300:364 )	A	300 - 364
7	X-RAY DIFFRACTION	7	( CHAIN B AND RESID 33:76 )	B	33 - 76
8	X-RAY DIFFRACTION	8	( CHAIN B AND RESID 77:153 )	B	77 - 153
9	X-RAY DIFFRACTION	9	( CHAIN B AND RESID 154:194 )	B	154 - 194
10	X-RAY DIFFRACTION	10	( CHAIN B AND RESID 195:241 )	B	195 - 241
11	X-RAY DIFFRACTION	11	( CHAIN B AND RESID 242:274 )	B	242 - 274
12	X-RAY DIFFRACTION	12	( CHAIN B AND RESID 275:299 )	B	275 - 299
13	X-RAY DIFFRACTION	13	( CHAIN B AND RESID 300:320 )	B	300 - 320
14	X-RAY DIFFRACTION	14	( CHAIN B AND RESID 321:347 )	B	321 - 347
15	X-RAY DIFFRACTION	15	( CHAIN B AND RESID 348:364 )	B	348 - 364

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