[English] 日本語
Yorodumi
- PDB-4k26: 4,4-Dioxo-5,6-dihydro-[1,4,3]oxathiazines, a novel class of 11 -H... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4k26
Title4,4-Dioxo-5,6-dihydro-[1,4,3]oxathiazines, a novel class of 11 -HSD1 inhibitors for the treatment of diabetes
ComponentsCorticosteroid 11-beta-dehydrogenase isozyme 1
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / Oxidoreductase / alpha and beta proteins / NAD(P)-binding Rossman-fold / short chain dehydrogenase / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


mineralocorticoid metabolic process / Glucocorticoid biosynthesis / glucocorticoid catabolic process / regulation of pentose-phosphate shunt / glucocorticoid biosynthetic process / 11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity ...mineralocorticoid metabolic process / Glucocorticoid biosynthesis / glucocorticoid catabolic process / regulation of pentose-phosphate shunt / glucocorticoid biosynthetic process / 11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Prednisone ADME / steroid catabolic process / steroid binding / lung development / apical part of cell / NADP binding / nuclear membrane / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / protein homodimerization activity
Similarity search - Function
short chain dehydrogenase / Short-chain dehydrogenase/reductase, conserved site / Short-chain dehydrogenases/reductases family signature. / Short-chain dehydrogenase/reductase SDR / NAD(P)-binding Rossmann-like Domain / NAD(P)-binding domain superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-NDP / Chem-SFF / 11-beta-hydroxysteroid dehydrogenase 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.21 Å
AuthorsLoenze, P. / Schimanski-Breves, S. / Vonderheyden, C. / Engel, C.K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2013
Title: 1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11-HSD1 inhibitors for the treatment of diabetes.
Authors: Bohme, T. / Engel, C.K. / Farjot, G. / Gussregen, S. / Haack, T. / Tschank, G. / Ritter, K.
History
DepositionApr 8, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 9, 2014Provider: repository / Type: Initial release
Revision 1.1Sep 20, 2023Group: 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_initial_refinement_model / 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 / _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: Corticosteroid 11-beta-dehydrogenase isozyme 1
B: Corticosteroid 11-beta-dehydrogenase isozyme 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,5239
Polymers61,1712
Non-polymers2,3527
Water4,558253
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8340 Å2
ΔGint-102 kcal/mol
Surface area21030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)133.864, 137.333, 70.557
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Corticosteroid 11-beta-dehydrogenase isozyme 1 / 11-beta-hydroxysteroid dehydrogenase 1 / 11-DH / 11-beta-HSD1 / 11beta-HSD1A


Mass: 30585.680 Da / Num. of mol.: 2 / Fragment: murine 11-BETA-HSD_24-292
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Hsd11b1, Hsd11 / Production host: ESCHERICHIA COLI (E. coli)
References: UniProt: P50172, 11beta-hydroxysteroid dehydrogenase
#2: Chemical ChemComp-SFF / (4aS,8aR)-N-cyclohexyl-4a,5,6,7,8,8a-hexahydro-4,1,2-benzoxathiazin-3-amine 1,1-dioxide


Mass: 286.390 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C13H22N2O3S
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 253 / 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: 2.65 Å3/Da / Density % sol: 53.59 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: HEPES 100mM pH 7.5, (NH4)2SO4 1.7M, 1 mM NADP, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 7, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2.21→95.82 Å / Num. obs: 32949 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Biso Wilson estimate: 27.85 Å2 / Rsym value: 0.127
Reflection shellResolution: 2.21→2.28 Å / Redundancy: 7.4 % / Mean I/σ(I) obs: 4.65 / Rsym value: 0.435 / % possible all: 100

-
Processing

Software
NameClassification
BUSTERrefinement
XDSdata reduction
XSCALEdata scaling
BUSTERphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1Y5R

1y5r


Resolution: 2.21→19.82 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.9178 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2082 1706 5.19 %RANDOM
Rwork0.1656 ---
obs0.1678 32890 99.95 %-
all-32967 --
Displacement parametersBiso mean: 27.56 Å2
Baniso -1Baniso -2Baniso -3
1--0.3718 Å20 Å20 Å2
2--0.1515 Å20 Å2
3---0.2203 Å2
Refine analyzeLuzzati coordinate error obs: 0.217 Å
Refinement stepCycle: LAST / Resolution: 2.21→19.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4078 0 149 253 4480
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014318HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.175835HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1577SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes83HARMONIC2
X-RAY DIFFRACTIONt_gen_planes648HARMONIC5
X-RAY DIFFRACTIONt_it4318HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.35
X-RAY DIFFRACTIONt_other_torsion18.25
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion585SEMIHARMONIC5
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_contact5449SEMIHARMONIC4
LS refinement shellResolution: 2.21→2.28 Å / Total num. of bins used: 16
RfactorNum. reflection% reflection
Rfree0.2625 148 4.95 %
Rwork0.1983 2843 -
all0.2014 2991 -
obs--99.95 %

+
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://pdbjlvh1.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