[English] 日本語
Yorodumi
- PDB-4npw: Crystal structure of human PDE1B bound to inhibitor 19A (7,8-dime... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4npw
TitleCrystal structure of human PDE1B bound to inhibitor 19A (7,8-dimethoxy-N-[(2S)-1-(3-methyl-1H-pyrazol-5-yl)propan-2-yl]quinazolin-4-amine)
ComponentsCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / cellular response to macrophage colony-stimulating factor stimulus / serotonin metabolic process / dopamine catabolic process / cellular response to granulocyte macrophage colony-stimulating factor stimulus / Cam-PDE 1 activation / 3',5'-cyclic-nucleotide phosphodiesterase / cGMP effects / 3',5'-cyclic-GMP phosphodiesterase activity ...calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / cellular response to macrophage colony-stimulating factor stimulus / serotonin metabolic process / dopamine catabolic process / cellular response to granulocyte macrophage colony-stimulating factor stimulus / Cam-PDE 1 activation / 3',5'-cyclic-nucleotide phosphodiesterase / cGMP effects / 3',5'-cyclic-GMP phosphodiesterase activity / monocyte differentiation / 3',5'-cyclic-AMP phosphodiesterase activity / response to amphetamine / locomotory behavior / visual learning / G alpha (s) signalling events / calmodulin binding / neuronal cell body / signal transduction / metal ion binding / cytosol
Similarity search - Function
3'5'-cyclic nucleotide phosphodiesterase N-terminal / 3'5'-cyclic nucleotide phosphodiesterase N-terminal / 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 N-terminal / 3'5'-cyclic nucleotide phosphodiesterase N-terminal / 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-0NY / Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsPandit, J. / Evdomikov, A. / Mansour, M. / Simons, S.
CitationJournal: MEDCHEMCOMM / Year: 2014
Title: Small-molecule phosphodiesterase probes: discovery of potent and selective CNS-penetrable quinazoline inhibitors of PDE1
Authors: Humphrey, J.M. / Yang, E.X. / Am Ende, C.W. / Arnold, E.P. / Head, J.L. / Jenkinsonb, S. / Lebel, L.A. / Liras, S. / Pandit, J. / Samas, B. / Vajdos, F. / Simons, S.P. / Evdokimova, A. / ...Authors: Humphrey, J.M. / Yang, E.X. / Am Ende, C.W. / Arnold, E.P. / Head, J.L. / Jenkinsonb, S. / Lebel, L.A. / Liras, S. / Pandit, J. / Samas, B. / Vajdos, F. / Simons, S.P. / Evdokimova, A. / Mansour, M. / Menniti, F.S.
History
DepositionNov 22, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 16, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn / 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_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.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_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_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_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: Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,5524
Polymers42,1351
Non-polymers4173
Water4,486249
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)88.782, 88.782, 134.806
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B / Cam-PDE 1B / 63 kDa Cam-PDE


Mass: 42134.945 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 142-507
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE1B, PDE1B1, PDES1B / Production host: ESCHERICHIA COLI (E. coli)
References: UniProt: Q01064, 3',5'-cyclic-nucleotide phosphodiesterase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-0NY / 7,8-dimethoxy-N-[(2S)-1-(3-methyl-1H-pyrazol-5-yl)propan-2-yl]quinazolin-4-amine


Mass: 327.381 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H21N5O2
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 249 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.15 Å3/Da / Density % sol: 60.98 %
Crystal growpH: 8.5
Details: 0.1 M TRIS-HCL, 0.2 M MGCL2, 125 UM 5-(5-BROMO-2-PROPOXYPHENYL)-3-PROPYL-1H-PYRAZOLO[4,3-D]PYRIMIDIN-7(6H)-ONE, 15% PEG 8000, PH 8.5, VAPOR DIFFUSION, TEMPERATURE 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.97872
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jun 27, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97872 Å / Relative weight: 1
ReflectionResolution: 1.9→50 Å / Num. obs: 42307 / % possible obs: 97.8 % / Redundancy: 8.1 % / Rmerge(I) obs: 0.101 / Net I/σ(I): 8
Reflection shellResolution: 1.9→1.97 Å / Redundancy: 8.3 % / Rmerge(I) obs: 0.774 / % possible all: 99.4

-
Processing

Software
NameVersionClassification
BUSTER2.11.2refinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→27.82 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.939 / SU R Cruickshank DPI: 0.11 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.209 2116 5.01 %RANDOM
Rwork0.19 ---
obs0.191 42246 97.9 %-
Displacement parametersBiso mean: 32.68 Å2
Baniso -1Baniso -2Baniso -3
1--2.7529 Å20 Å20 Å2
2---2.7529 Å20 Å2
3---5.5057 Å2
Refine analyzeLuzzati coordinate error obs: 0.21 Å
Refinement stepCycle: LAST / Resolution: 1.9→27.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2597 0 26 249 2872
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012679HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.953629HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d938SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes66HARMONIC2
X-RAY DIFFRACTIONt_gen_planes388HARMONIC5
X-RAY DIFFRACTIONt_it2679HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion2.73
X-RAY DIFFRACTIONt_other_torsion16.88
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion357SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3402SEMIHARMONIC4
LS refinement shellResolution: 1.9→1.95 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2331 174 5.61 %
Rwork0.2094 2930 -
all0.2107 3104 -
obs--97.89 %

+
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