[English] 日本語
Yorodumi
- PDB-9ba9: O-GlcNAcase (OGA) inhibitor complex for the Treatment of Alzheime... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ba9
TitleO-GlcNAcase (OGA) inhibitor complex for the Treatment of Alzheimer's Disease
ComponentsProtein O-GlcNAcase
KeywordsHYDROLASE / Inhibitor / Complex / O-GlcNAcase
Function / homology
Function and homology information


glycoprotein metabolic process / hyalurononglucosaminidase activity / N-acetylglucosamine metabolic process / protein O-GlcNAcase / protein deglycosylation / [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity / glycoprotein catabolic process / protein O-linked glycosylation / beta-N-acetylglucosaminidase activity / identical protein binding ...glycoprotein metabolic process / hyalurononglucosaminidase activity / N-acetylglucosamine metabolic process / protein O-GlcNAcase / protein deglycosylation / [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity / glycoprotein catabolic process / protein O-linked glycosylation / beta-N-acetylglucosaminidase activity / identical protein binding / nucleus / membrane / cytosol
Similarity search - Function
Beta-N-acetylglucosaminidase / beta-N-acetylglucosaminidase / Glycosyl hydrolases family 84 (GH84) domain profile. / : / Acyl-CoA N-acyltransferase / Glycoside hydrolase superfamily
Similarity search - Domain/homology
: / Protein O-GlcNAcase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.75 Å
AuthorsHendle, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Alzheimers Dement (N Y) / Year: 2024
Title: Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.
Authors: Kielbasa, W. / Goldsmith, P. / Donnelly, K.B. / Nuthall, H.N. / Shcherbinin, S. / Fleisher, A.S. / Hendle, J. / DuBois, S.L. / Lowe, S.L. / Zhang, F.F. / Woerly, E.M. / Dreyfus, N.J. / ...Authors: Kielbasa, W. / Goldsmith, P. / Donnelly, K.B. / Nuthall, H.N. / Shcherbinin, S. / Fleisher, A.S. / Hendle, J. / DuBois, S.L. / Lowe, S.L. / Zhang, F.F. / Woerly, E.M. / Dreyfus, N.J. / Evans, D. / Gilmore, J. / Mancini, M. / Constantinescu, C.C. / Gunn, R.N. / Russell, D.S. / Collins, E.C. / Brys, M. / Hutton, M.L. / Mergott, D.J.
History
DepositionApr 3, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 15, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein O-GlcNAcase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)61,5722
Polymers61,3331
Non-polymers2391
Water66737
1
A: Protein O-GlcNAcase
hetero molecules

A: Protein O-GlcNAcase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)123,1444
Polymers122,6652
Non-polymers4792
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_554-y,-x,-z-1/21
Buried area7960 Å2
ΔGint-50 kcal/mol
Surface area36360 Å2
MethodPISA
Unit cell
Length a, b, c (Å)133.261, 133.261, 114.236
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein Protein O-GlcNAcase / OGA / Beta-N-acetylglucosaminidase / Beta-N-acetylhexosaminidase / Beta-hexosaminidase / Meningioma- ...OGA / Beta-N-acetylglucosaminidase / Beta-N-acetylhexosaminidase / Beta-hexosaminidase / Meningioma-expressed antigen 5 / N-acetyl-beta-D-glucosaminidase / N-acetyl-beta-glucosaminidase / Nuclear cytoplasmic O-GlcNAcase and acetyltransferase / NCOAT


Mass: 61332.586 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: OGA, HEXC, KIAA0679, MEA5, MGEA5 / Production host: Escherichia coli (E. coli) / References: UniProt: O60502, protein O-GlcNAcase
#2: Chemical ChemComp-A1AKL / N-{5-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl}acetamide


Mass: 239.337 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H17N3OS / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 37 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.13 Å3/Da / Density % sol: 70.25 %
Crystal growTemperature: 281 K / Method: vapor diffusion, sitting drop / pH: 8.5 / Details: 33% PEG 300, 100mM Hepes pH 8.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97931 Å
DetectorType: RAYONIX MX225HE / Detector: CCD / Date: Dec 7, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97931 Å / Relative weight: 1
ReflectionResolution: 2.75→53 Å / Num. obs: 27328 / % possible obs: 100 % / Redundancy: 8.6 % / Rmerge(I) obs: 0.103 / Net I/σ(I): 4.6
Reflection shellResolution: 2.75→2.9 Å / Redundancy: 8.8 % / Rmerge(I) obs: 0.536 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 3932 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.7.0029refinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.75→30 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.911 / SU B: 11.897 / SU ML: 0.23 / Cross valid method: THROUGHOUT / ESU R: 0.355 / ESU R Free: 0.277 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.26023 1371 5 %RANDOM
Rwork0.21729 ---
obs0.2194 25791 99.34 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 74.774 Å2
Baniso -1Baniso -2Baniso -3
1--4.99 Å2-0 Å2-0 Å2
2---4.99 Å20 Å2
3---9.97 Å2
Refinement stepCycle: 1 / Resolution: 2.75→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3633 0 16 37 3686
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0193773
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.0091.9615129
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.9355463
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.44523.179173
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.22515597
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.0921527
X-RAY DIFFRACTIONr_chiral_restr0.0710.2551
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212911
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.75→2.821 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.381 99 -
Rwork0.36 1882 -
obs--99.85 %

+
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