[English] 日本語
Yorodumi
- PDB-8fd8: human 15-PGDH with NADH bound -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fd8
Titlehuman 15-PGDH with NADH bound
Components15-hydroxyprostaglandin dehydrogenase [NAD(+)]
KeywordsOXIDOREDUCTASE / DEHYDROGENASE / INHIBITOR / OXIDOREDUCTASE-INHIBITOR complex
Function / homology
Function and homology information


15-hydroxyprostaglandin dehydrogenase (NAD+) / 15-hydroxyicosatetraenoate dehydrogenase / regulation of prostaglandin catabolic process / ductus arteriosus closure / thrombin-activated receptor signaling pathway / ovulation / prostaglandin E receptor activity / 15-hydroxyprostaglandin dehydrogenase (NAD+) activity / Synthesis of Lipoxins (LX) / parturition ...15-hydroxyprostaglandin dehydrogenase (NAD+) / 15-hydroxyicosatetraenoate dehydrogenase / regulation of prostaglandin catabolic process / ductus arteriosus closure / thrombin-activated receptor signaling pathway / ovulation / prostaglandin E receptor activity / 15-hydroxyprostaglandin dehydrogenase (NAD+) activity / Synthesis of Lipoxins (LX) / parturition / lipoxygenase pathway / Biosynthesis of D-series resolvins / Biosynthesis of E-series 18(S)-resolvins / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor / prostaglandin metabolic process / negative regulation of cell cycle / NAD+ binding / positive regulation of vascular associated smooth muscle cell proliferation / transforming growth factor beta receptor signaling pathway / kidney development / female pregnancy / NAD binding / response to estradiol / basolateral plasma membrane / response to ethanol / response to lipopolysaccharide / positive regulation of apoptotic process / extracellular exosome / nucleoplasm / identical protein binding / cytosol / cytoplasm
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 domain superfamily
Similarity search - Domain/homology
1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / 15-hydroxyprostaglandin dehydrogenase [NAD(+)]
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsHuang, W. / Taylor, D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1RM1GM142002 United States
CitationJournal: Nat Commun / Year: 2023
Title: Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system.
Authors: Wei Huang / Hongyun Li / Janna Kiselar / Stephen P Fink / Sagar Regmi / Alexander Day / Yiyuan Yuan / Mark Chance / Joseph M Ready / Sanford D Markowitz / Derek J Taylor /
Abstract: 15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem ...15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem cells during tissue repair. Indeed, inhibiting 15-PGDH markedly accelerates tissue repair in multiple organs. Here we have used cryo-electron microscopy to solve the solution structure of native 15-PGDH and of 15-PGDH individually complexed with two distinct chemical inhibitors. These structures identify key 15-PGDH residues that mediate binding to both classes of inhibitors. Moreover, we identify a dynamic 15-PGDH lid domain that closes around the inhibitors, and that is likely fundamental to the physiologic 15-PGDH enzymatic mechanism. We furthermore identify two key residues, F185 and Y217, that act as hinges to regulate lid closing, and which both inhibitors exploit to capture the lid in the closed conformation, thus explaining their sub-nanomolar binding affinities. These findings provide the basis for further development of 15-PGDH targeted drugs as therapeutics for regenerative medicine.
History
DepositionDec 2, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 8, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 15-hydroxyprostaglandin dehydrogenase [NAD(+)]
B: 15-hydroxyprostaglandin dehydrogenase [NAD(+)]
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,1034
Polymers55,7722
Non-polymers1,3312
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein 15-hydroxyprostaglandin dehydrogenase [NAD(+)] / 15-PGDH / Eicosanoid/docosanoid dehydrogenase [NAD(+)] / Prostaglandin dehydrogenase 1 / Short ...15-PGDH / Eicosanoid/docosanoid dehydrogenase [NAD(+)] / Prostaglandin dehydrogenase 1 / Short chain dehydrogenase/reductase family 36C member 1


Mass: 27886.053 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HPGD, PGDH1, SDR36C1 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P15428, 15-hydroxyprostaglandin dehydrogenase (NAD+), Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor, 15-hydroxyicosatetraenoate dehydrogenase
#2: Chemical ChemComp-NAI / 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / NADH / Nicotinamide adenine dinucleotide


Mass: 665.441 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H29N7O14P2
Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: HUMAN 15-PGDH IN COMPLEX WITH INHIBITOR / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2000 nm / Nominal defocus min: 250 nm
Image recordingElectron dose: 1.08 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.20.1_4487: / Classification: refinement
Image processing
IDImage recording-ID
11
21
CTF correction
IDEM image processing-IDType
11PHASE FLIPPING AND AMPLITUDE CORRECTION
22PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstruction

Entry-ID: 8FD8 / Num. of particles: 267049 / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Symmetry type: POINT

IDImage processing-IDNum. of class averages
111
211
32
42
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 51.83 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0028070
ELECTRON MICROSCOPYf_angle_d0.87114618
ELECTRON MICROSCOPYf_dihedral_angle_d12.4552204
ELECTRON MICROSCOPYf_chiral_restr0.056632
ELECTRON MICROSCOPYf_plane_restr0.0021202

+
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