Full wwPDB X-ray Structure Validation Report i○

Apr 14, 2019 – 12:27 AM EDT

PDB ID : 6IJHTitle : Crystal structure of PDE10 in complex with inhibitor AF-399/14387019

Authors : Huang, Y.Y.; Yu, Y.F.; Zhang, C.; Wu, D.; Wu, Y.; Luo, H.B.Deposited on : 2018-10-10

Resolution : 2.60 Å(reported)

This is a Full wwPDB X-ray Structure Validation Report for a publicly released PDB entry.

We welcome your comments at validation@mail.wwpdb.orgA user guide is available at

https://www.wwpdb.org/validation/2017/XrayValidationReportHelpwith specific help available everywhere you see the i○ symbol.

The following versions of software and data (see references i○) were used in the production of this report:

MolProbity : 4.02b-467Mogul : 1.8.0 (224370), CSD as540be (2019)

Xtriage (Phenix) : 1.13EDS : rb-20031633

Percentile statistics : 20171227.v01 (using entries in the PDB archive December 27th 2017)Refmac : 5.8.0158CCP4 : 7.0 (Gargrove)

Ideal geometry (proteins) : Engh & Huber (2001)Ideal geometry (DNA, RNA) : Parkinson et al. (1996)

Validation Pipeline (wwPDB-VP) : rb-20031633

Page 2 Full wwPDB X-ray Structure Validation Report 6IJH

1 Overall quality at a glance i○

The following experimental techniques were used to determine the structure:X-RAY DIFFRACTION

The reported resolution of this entry is 2.60 Å.

Percentile scores (ranging between 0-100) for global validation metrics of the entry are shown inthe following graphic. The table shows the number of entries on which the scores are based.

Metric Whole archive(#Entries)

Similar resolution(#Entries, resolution range(Å))

Rfree 111664 2767 (2.60-2.60)Clashscore 122126 3110 (2.60-2.60)

Ramachandran outliers 120053 3062 (2.60-2.60)Sidechain outliers 120020 3062 (2.60-2.60)RSRZ outliers 108989 2706 (2.60-2.60)

The table below summarises the geometric issues observed across the polymeric chains and their fitto the electron density. The red, orange, yellow and green segments on the lower bar indicate thefraction of residues that contain outliers for >=3, 2, 1 and 0 types of geometric quality criteria. Agrey segment represents the fraction of residues that are not modelled. The numeric value for eachfraction is indicated below the corresponding segment, with a dot representing fractions <=5%The upper red bar (where present) indicates the fraction of residues that have poor fit to theelectron density. The numeric value is given above the bar.

Mol Chain Length Quality of chain

1 A 343

1 B 343

Page 3 Full wwPDB X-ray Structure Validation Report 6IJH

2 Entry composition i○

There are 5 unique types of molecules in this entry. The entry contains 5346 atoms, of which 0are hydrogens and 0 are deuteriums.

In the tables below, the ZeroOcc column contains the number of atoms modelled with zero occu-pancy, the AltConf column contains the number of residues with at least one atom in alternateconformation and the Trace column contains the number of residues modelled with at most 2atoms.

• Molecule 1 is a protein called cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodi-esterase 10A.

Mol Chain Residues Atoms ZeroOcc AltConf Trace

1 A 322 Total C N O S2611 1668 445 473 25 0 0 0

1 B 322 Total C N O S2610 1667 443 475 25 0 0 0

There are 4 discrepancies between the modelled and reference sequences:

Chain Residue Modelled Actual Comment ReferenceA 447 HIS - expression tag UNP Q9Y233A 448 MET - expression tag UNP Q9Y233B 447 HIS - expression tag UNP Q9Y233B 448 MET - expression tag UNP Q9Y233

• Molecule 2 is ZINC ION (three-letter code: ZN) (formula: Zn).

Mol Chain Residues Atoms ZeroOcc AltConf

2 B 1 Total Zn1 1 0 0

2 A 1 Total Zn1 1 0 0

• Molecule 3 is MAGNESIUM ION (three-letter code: MG) (formula: Mg).

Mol Chain Residues Atoms ZeroOcc AltConf

3 B 1 Total Mg1 1 0 0

3 A 1 Total Mg1 1 0 0

• Molecule 4 is 2-[2-(4-phenyl-5-sulfanylidene-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (three-letter code: AEO) (formula: C22H16N4O2S).

Page 4 Full wwPDB X-ray Structure Validation Report 6IJH

Mol Chain Residues Atoms ZeroOcc AltConf

4 A 1 Total C N O S29 22 4 2 1 0 0

4 B 1 Total C N O S29 22 4 2 1 0 0

• Molecule 5 is water.

Mol Chain Residues Atoms ZeroOcc AltConf

5 A 21 Total O21 21 0 0

5 B 42 Total O42 42 0 0

Page 5 Full wwPDB X-ray Structure Validation Report 6IJH

3 Residue-property plots i○

These plots are drawn for all protein, RNA and DNA chains in the entry. The first graphic fora chain summarises the proportions of the various outlier classes displayed in the second graphic.The second graphic shows the sequence view annotated by issues in geometryand electron density.Residues are color-coded according to the number of geometric quality criteria for which theycontain at least one outlier: green = 0, yellow = 1, orange = 2 and red = 3 or more. A red dotabove a residue indicates a poor fit to the electron density (RSRZ > 2). Stretches of 2 or moreconsecutive residues without any outlier are shown as a green connector. Residues present in thesample, but not in the model, are shown in grey.

• Molecule 1: cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A

Chain A:

H447•

L464

I472

E483

N484

M485

W486

D550•

D579•

L585

I610

T651•

N657•

N658

A672

L675

V678

K686

Q709

Y730

A734

I735

P736

L741

S760

G768

GLU

GLU

THR

ALA

THR

TRP

ILE

SER

SER

PRO

SER

VAL

ALA

GLN

LYS

ALA

ALA

ALA

SER

GLU

ASP

• Molecule 1: cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A

Chain B:

HIS

M448•

S449•

I450•

C451•

T452•

S453•

E454•

E455•

W456•

Q457•

G458•

F462•

T463•

L464

R467

I472

E483

N484

M485

W486

H495

T500

V515

L565

D579

A584•

L585•

V622

R642

N655

L656•

N657

N658

H661

L675

V678

L687•

I711•

L727

Y730

A734

L759

S760

E769

GLU

THR

ALA

THR

TRP

ILE

SER

SER

PRO

SER

VAL

ALA

GLN

LYS

ALA

ALA

ALA

SER

GLU

ASP

Page 6 Full wwPDB X-ray Structure Validation Report 6IJH

4 Data and refinement statistics i○

Property Value SourceSpace group P 21 21 21 DepositorCell constantsa, b, c, α, β, γ

49.34Å 81.69Å 159.82Å90.00◦ 90.00◦ 90.00◦ Depositor

Resolution (Å) 79.91 – 2.6023.84 – 2.60

DepositorEDS

% Data completeness(in resolution range)

99.6 (79.91-2.60)99.8 (23.84-2.60)

DepositorEDS

Rmerge 0.09 DepositorRsym (Not available) Depositor

< I/σ(I) > 1 1.82 (at 2.60Å) XtriageRefinement program REFMAC 5.8.0189 Depositor

R, Rfree0.240 , 0.3120.243 , 0.310

DepositorDCC

Rfree test set 1012 reflections (4.93%) wwPDB-VPWilson B-factor (Å2) 33.7 Xtriage

Anisotropy 0.054 XtriageBulk solvent ksol(e/Å3), Bsol(Å2) 0.32 , 29.2 EDS

L-test for twinning2 < |L| > = 0.39, < L2 > = 0.21 XtriageEstimated twinning fraction No twinning to report. Xtriage

Fo,Fc correlation 0.88 EDSTotal number of atoms 5346 wwPDB-VP

Average B, all atoms (Å2) 37.0 wwPDB-VP

Xtriage’s analysis on translational NCS is as follows: The largest off-origin peak in the Pattersonfunction is 4.26% of the height of the origin peak. No significant pseudotranslation is detected.

1Intensities estimated from amplitudes.2Theoretical values of < |L| >, < L2 > for acentric reflections are 0.5, 0.333 respectively for untwinned datasets,

and 0.375, 0.2 for perfectly twinned datasets.

Page 7 Full wwPDB X-ray Structure Validation Report 6IJH

5 Model quality i○

5.1 Standard geometry i○

Bond lengths and bond angles in the following residue types are not validated in this section: MG,ZN, AEO

The Z score for a bond length (or angle) is the number of standard deviations the observed valueis removed from the expected value. A bond length (or angle) with |Z| > 5 is considered anoutlier worth inspection. RMSZ is the root-mean-square of all Z scores of the bond lengths (orangles).

Mol Chain Bond lengths Bond anglesRMSZ #|Z| >5 RMSZ #|Z| >5

1 A 0.41 0/2676 0.57 0/36231 B 0.41 0/2674 0.57 0/3620All All 0.41 0/5350 0.57 0/7243

There are no bond length outliers.

There are no bond angle outliers.

There are no chirality outliers.

There are no planarity outliers.

5.2 Too-close contacts i○

In the following table, the Non-H and H(model) columns list the number of non-hydrogen atomsand hydrogen atoms in the chain respectively. The H(added) column lists the number of hydrogenatoms added and optimized by MolProbity. The Clashes column lists the number of clashes withinthe asymmetric unit, whereas Symm-Clashes lists symmetry related clashes.

Mol Chain Non-H H(model) H(added) Clashes Symm-Clashes1 A 2611 0 2576 6 01 B 2610 0 2575 8 02 A 1 0 0 0 02 B 1 0 0 0 03 A 1 0 0 0 03 B 1 0 0 0 04 A 29 0 0 1 04 B 29 0 0 0 05 A 21 0 0 0 05 B 42 0 0 0 0All All 5346 0 5151 15 0

Page 8 Full wwPDB X-ray Structure Validation Report 6IJH

The all-atom clashscore is defined as the number of clashes found per 1000 atoms (includinghydrogen atoms). The all-atom clashscore for this structure is 1.

All (15) close contacts within the same asymmetric unit are listed below, sorted by their clashmagnitude.

Atom-1 Atom-2 Interatomicdistance (Å)

Clashoverlap (Å)

1:A:464:LEU:HD21 1:A:472:ILE:HD12 1.77 0.661:B:464:LEU:HD21 1:B:472:ILE:HD12 1.82 0.601:B:675:LEU:O 1:B:678:VAL:HG22 2.01 0.60

4:A:803:AEO:O14 4:A:803:AEO:C17 2.53 0.571:A:730:TYR:HA 1:A:734:ALA:HB3 1.99 0.451:A:735:ILE:HB 1:A:736:PRO:HD3 1.98 0.451:B:730:TYR:HA 1:B:734:ALA:HB3 2.00 0.441:A:675:LEU:O 1:A:678:VAL:HG22 2.18 0.44

1:B:727:LEU:HD12 1:B:759:LEU:HD12 2.00 0.441:B:495:HIS:ND1 1:B:500:THR:HG22 2.33 0.431:B:515:VAL:HG13 1:B:565:LEU:HD21 2.00 0.421:A:483:GLU:HA 1:A:486:TRP:CE2 2.54 0.421:B:484:ASN:HD22 1:B:484:ASN:N 2.17 0.421:B:483:GLU:HA 1:B:486:TRP:CE2 2.54 0.411:A:672:ALA:CB 1:A:741:LEU:HD22 2.51 0.41

There are no symmetry-related clashes.

5.3 Torsion angles i○

5.3.1 Protein backbone i○

In the following table, the Percentiles column shows the percent Ramachandran outliers of thechain as a percentile score with respect to all X-ray entries followed by that with respect to entriesof similar resolution.

The Analysed column shows the number of residues for which the backbone conformation wasanalysed, and the total number of residues.

Mol Chain Analysed Favoured Allowed Outliers Percentiles

1 A 320/343 (93%) 307 (96%) 12 (4%) 1 (0%) 43 68

1 B 320/343 (93%) 309 (97%) 10 (3%) 1 (0%) 43 68

All All 640/686 (93%) 616 (96%) 22 (3%) 2 (0%) 43 68

All (2) Ramachandran outliers are listed below:

Page 9 Full wwPDB X-ray Structure Validation Report 6IJH

Mol Chain Res Type1 B 579 ASP1 A 579 ASP

5.3.2 Protein sidechains i○

In the following table, the Percentiles column shows the percent sidechain outliers of the chain as apercentile score with respect to all X-ray entries followed by that with respect to entries of similarresolution.

The Analysed column shows the number of residues for which the sidechain conformation wasanalysed, and the total number of residues.

Mol Chain Analysed Rotameric Outliers Percentiles

1 A 291/307 (95%) 282 (97%) 9 (3%) 43 70

1 B 291/307 (95%) 281 (97%) 10 (3%) 40 67

All All 582/614 (95%) 563 (97%) 19 (3%) 41 68

All (19) residues with a non-rotameric sidechain are listed below:

Mol Chain Res Type1 A 447 HIS1 A 484 ASN1 A 585 LEU1 A 610 ILE1 A 657 ASN1 A 658 ASN1 A 686 LYS1 A 709 GLN1 A 760 SER1 B 467 ARG1 B 484 ASN1 B 585 LEU1 B 622 VAL1 B 642 ARG1 B 655 ASN1 B 657 ASN1 B 658 ASN1 B 661 HIS1 B 760 SER

Some sidechains can be flipped to improve hydrogen bonding and reduce clashes. All (11) suchsidechains are listed below:

Page 10 Full wwPDB X-ray Structure Validation Report 6IJH

Mol Chain Res Type1 A 641 ASN1 A 657 ASN1 A 658 ASN1 A 659 GLN1 A 690 ASN1 A 724 GLN1 B 484 ASN1 B 641 ASN1 B 655 ASN1 B 657 ASN1 B 658 ASN

5.3.3 RNA i○

There are no RNA molecules in this entry.

5.4 Non-standard residues in protein, DNA, RNA chains i○

There are no non-standard protein/DNA/RNA residues in this entry.

5.5 Carbohydrates i○

There are no carbohydrates in this entry.

5.6 Ligand geometry i○

Of 6 ligands modelled in this entry, 4 are monoatomic - leaving 2 for Mogul analysis.

In the following table, the Counts columns list the number of bonds (or angles) for which Mogulstatistics could be retrieved, the number of bonds (or angles) that are observed in the model andthe number of bonds (or angles) that are defined in the Chemical Component Dictionary. TheLink column lists molecule types, if any, to which the group is linked. The Z score for a bondlength (or angle) is the number of standard deviations the observed value is removed from theexpected value. A bond length (or angle) with |Z| > 2 is considered an outlier worth inspection.RMSZ is the root-mean-square of all Z scores of the bond lengths (or angles).

Mol Type Chain Res Link Bond lengths Bond anglesCounts RMSZ #|Z| > 2 Counts RMSZ #|Z| > 2

4 AEO A 803 - 32,33,33 1.29 3 (9%) 28,48,48 1.11 1 (3%)4 AEO B 803 - 32,33,33 1.25 2 (6%) 28,48,48 1.09 1 (3%)

Page 11 Full wwPDB X-ray Structure Validation Report 6IJH

In the following table, the Chirals column lists the number of chiral outliers, the number of chiralcenters analysed, the number of these observed in the model and the number defined in theChemical Component Dictionary. Similar counts are reported in the Torsion and Rings columns.’-’ means no outliers of that kind were identified.

Mol Type Chain Res Link Chirals Torsions Rings4 AEO A 803 - - 0/9/9/9 0/5/5/54 AEO B 803 - - 0/9/9/9 0/5/5/5

All (5) bond length outliers are listed below:

Mol Chain Res Type Atoms Z Observed(Å) Ideal(Å)4 A 803 AEO C18-N19 2.32 1.40 1.374 B 803 AEO C11-C5 3.77 1.48 1.414 A 803 AEO C11-C5 3.78 1.48 1.414 A 803 AEO C13-C7 3.82 1.48 1.414 B 803 AEO C13-C7 3.85 1.48 1.41

All (2) bond angle outliers are listed below:

Mol Chain Res Type Atoms Z Observed(o) Ideal(o)4 B 803 AEO C20-N21-N22 4.29 113.90 105.414 A 803 AEO C20-N21-N22 4.32 113.97 105.41

There are no chirality outliers.

There are no torsion outliers.

There are no ring outliers.

1 monomer is involved in 1 short contact:

Mol Chain Res Type Clashes Symm-Clashes4 A 803 AEO 1 0

5.7 Other polymers i○

There are no such residues in this entry.

5.8 Polymer linkage issues i○

There are no chain breaks in this entry.

Page 12 Full wwPDB X-ray Structure Validation Report 6IJH

6 Fit of model and data i○

6.1 Protein, DNA and RNA chains i○

In the following table, the column labelled ‘#RSRZ> 2’ contains the number (and percentage)of RSRZ outliers, followed by percent RSRZ outliers for the chain as percentile scores relative toall X-ray entries and entries of similar resolution. The OWAB column contains the minimum,median, 95th percentile and maximum values of the occupancy-weighted average B-factor perresidue. The column labelled ‘Q< 0.9’ lists the number of (and percentage) of residues with anaverage occupancy less than 0.9.

Mol Chain Analysed <RSRZ> #RSRZ>2 OWAB(Å2) Q<0.9

1 A 322/343 (93%) 0.03 5 (1%) 72 67 18, 35, 52, 70 0

1 B 322/343 (93%) 0.23 18 (5%) 24 18 16, 38, 61, 92 0

All All 644/686 (93%) 0.13 23 (3%) 42 35 16, 36, 57, 92 0

All (23) RSRZ outliers are listed below:

Mol Chain Res Type RSRZ1 B 458 GLY 4.61 B 452 THR 4.21 B 451 CYS 3.61 B 453 SER 3.51 A 657 ASN 3.51 A 447 HIS 3.41 B 456 TRP 3.41 B 455 GLU 3.11 A 651 THR 3.01 B 450 ILE 3.01 B 454 GLU 2.91 B 584 ALA 2.71 B 585 LEU 2.71 B 687 LEU 2.71 B 462 PHE 2.51 B 449 SER 2.41 A 550 ASP 2.31 B 463 THR 2.31 A 579 ASP 2.21 B 457 GLN 2.21 B 656 LEU 2.11 B 448 MET 2.11 B 711 ILE 2.1

Page 13 Full wwPDB X-ray Structure Validation Report 6IJH

6.2 Non-standard residues in protein, DNA, RNA chains i○

There are no non-standard protein/DNA/RNA residues in this entry.

6.3 Carbohydrates i○

There are no carbohydrates in this entry.

6.4 Ligands i○

In the following table, the Atoms column lists the number of modelled atoms in the group and thenumber defined in the chemical component dictionary. The B-factors column lists the minimum,median, 95th percentile and maximum values of B factors of atoms in the group. The columnlabelled ‘Q< 0.9’ lists the number of atoms with occupancy less than 0.9.

Mol Type Chain Res Atoms RSCC RSR B-factors(Å2) Q<0.94 AEO A 803 29/29 0.86 0.23 51,56,58,60 04 AEO B 803 29/29 0.93 0.14 25,27,29,30 03 MG B 802 1/1 0.96 0.10 13,13,13,13 03 MG A 802 1/1 0.97 0.16 21,21,21,21 02 ZN B 801 1/1 0.99 0.03 51,51,51,51 02 ZN A 801 1/1 1.00 0.02 31,31,31,31 0

6.5 Other polymers i○

There are no such residues in this entry.