[English] 日本語
Yorodumi
- PDB-4g2l: Human PDE9 in complex with selective compound -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4g2l
TitleHuman PDE9 in complex with selective compound
ComponentsHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
KeywordsHYDROLASE/HYDROLASE INHIBITOR / phosphodiesterase / inhibitor complex / cGMP->GMP / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


cGMP metabolic process / negative regulation of neural precursor cell proliferation / 3',5'-cyclic-GMP phosphodiesterase / cGMP catabolic process / positive regulation of cardiac muscle hypertrophy / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling ...cGMP metabolic process / negative regulation of neural precursor cell proliferation / 3',5'-cyclic-GMP phosphodiesterase / cGMP catabolic process / positive regulation of cardiac muscle hypertrophy / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling / positive regulation of long-term synaptic potentiation / sarcolemma / ruffle membrane / perikaryon / perinuclear region of cytoplasm / Golgi apparatus / signal transduction / endoplasmic reticulum / nucleoplasm / identical protein binding / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase, conserved site / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase domain signature. / 3'5'-cyclic nucleotide phosphodiesterase domain profile. / Metal dependent phosphohydrolases with conserved 'HD' motif. ...Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase, conserved site / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase domain signature. / 3'5'-cyclic nucleotide phosphodiesterase domain profile. / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-0WL / High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 3 Å
AuthorsLiu, S.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors.
Authors: Claffey, M.M. / Helal, C.J. / Verhoest, P.R. / Kang, Z. / Fors, K.S. / Jung, S. / Zhong, J. / Bundesmann, M.W. / Hou, X. / Lui, S. / Kleiman, R.J. / Vanase-Frawley, M. / Schmidt, A.W. / ...Authors: Claffey, M.M. / Helal, C.J. / Verhoest, P.R. / Kang, Z. / Fors, K.S. / Jung, S. / Zhong, J. / Bundesmann, M.W. / Hou, X. / Lui, S. / Kleiman, R.J. / Vanase-Frawley, M. / Schmidt, A.W. / Menniti, F. / Schmidt, C.J. / Hoffman, W.E. / Hajos, M. / McDowell, L. / O'Connor, R.E. / Macdougall-Murphy, M. / Fonseca, K.R. / Becker, S.L. / Nelson, F.R. / Liras, S.
History
DepositionJul 12, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 29, 2013Provider: repository / Type: Initial release
Revision 1.1Feb 28, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn / struct_ncs_dom_lim / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
B: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)78,6368
Polymers77,7262
Non-polymers9106
Water00
1
A: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,3184
Polymers38,8631
Non-polymers4553
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,3184
Polymers38,8631
Non-polymers4553
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
A: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
hetero molecules

B: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)78,6368
Polymers77,7262
Non-polymers9106
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_645-y+3/2,x-1/2,z+1/41
Buried area2840 Å2
ΔGint-111 kcal/mol
Surface area28330 Å2
MethodPISA
Unit cell
Length a, b, c (Å)104.226, 104.226, 270.476
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Ens-ID: 1 / Refine code: 2

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11GLYGLYGLNGLNAA178 - 4271 - 250
21GLYGLYGLNGLNBB178 - 4271 - 250
12THRTHRASPASPAA448 - 488271 - 311
22THRTHRASPASPBB448 - 488271 - 311

-
Components

#1: Protein High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A


Mass: 38862.926 Da / Num. of mol.: 2 / Fragment: UNP Residues 242-566
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE9A
References: UniProt: O76083, 3',5'-cyclic-GMP phosphodiesterase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-0WL / 1-cyclopentyl-6-{(1R)-1-[3-(pyrimidin-2-yl)azetidin-1-yl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one


Mass: 365.432 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H23N7O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 4.73 Å3/Da / Density % sol: 73.97 %

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3→50 Å / Num. all: 30918 / Num. obs: 30608 / % possible obs: 99 % / Observed criterion σ(I): 2

-
Processing

SoftwareName: REFMAC / Version: 5.2.0019 / Classification: refinement
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 3→49.81 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.916 / SU B: 25.322 / SU ML: 0.199 / Cross valid method: THROUGHOUT / ESU R: 0.567 / ESU R Free: 0.299 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21439 3148 10.3 %RANDOM
Rwork0.18244 ---
obs0.18585 27383 99.15 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 37.088 Å2
Baniso -1Baniso -2Baniso -3
1-1.76 Å20 Å20 Å2
2--1.76 Å20 Å2
3----3.52 Å2
Refinement stepCycle: LAST / Resolution: 3→49.81 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5412 0 58 0 5470
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0210.0225614
X-RAY DIFFRACTIONr_bond_other_d0.0020.023842
X-RAY DIFFRACTIONr_angle_refined_deg1.8691.9667608
X-RAY DIFFRACTIONr_angle_other_deg1.05839362
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1895654
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.57824.317278
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.731151000
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.4011532
X-RAY DIFFRACTIONr_chiral_restr0.0920.2814
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.026176
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021140
X-RAY DIFFRACTIONr_nbd_refined0.2530.21448
X-RAY DIFFRACTIONr_nbd_other0.1980.23896
X-RAY DIFFRACTIONr_nbtor_refined0.2050.22801
X-RAY DIFFRACTIONr_nbtor_other0.0980.22904
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.140.283
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.270.213
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2650.229
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.220.25
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.8621.54211
X-RAY DIFFRACTIONr_mcbond_other0.1391.51288
X-RAY DIFFRACTIONr_mcangle_it1.03925380
X-RAY DIFFRACTIONr_scbond_it1.8932700
X-RAY DIFFRACTIONr_scangle_it2.9434.52224
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Dom-ID: 1 / Auth asym-ID: A / Ens-ID: 1 / Refine-ID: X-RAY DIFFRACTION

NumberTypeRms dev position (Å)Weight position
1723tight positional0.060.05
2334medium positional0.320.5
1723tight thermal0.110.5
2334medium thermal0.542
LS refinement shellResolution: 3→3.078 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.313 195 -
Rwork0.312 2042 -
obs--99.55 %
Refinement TLS params.

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

IDL11 (°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)
11.2935-0.4734-0.14461.40990.20371.77110.0631-0.0860.0580.0452-0.02860.1823-0.2087-0.1372-0.0345-0.00690.003-0.0036-0.1939-0.0009-0.090884.6645.816945.6683
20.8628-0.31130.31331.5517-0.24391.84160.02330.1502-0.0991-0.0659-0.0562-0.01010.15880.07670.0329-0.10710.02770.0288-0.1147-0.0157-0.087193.139832.00326.8966
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A181 - 505
2X-RAY DIFFRACTION1A901 - 903
3X-RAY DIFFRACTION2B181 - 505
4X-RAY DIFFRACTION2B901 - 903

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more