[English] 日本語
Yorodumi
- PDB-8gks: Human mitochondrial serine hydroxymethyltransferase (SHMT2) in co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8gks
TitleHuman mitochondrial serine hydroxymethyltransferase (SHMT2) in complex with PLP, glycine and AGF291 inhibitor
ComponentsSerine hydroxymethyltransferase, mitochondrial
KeywordsTRANSFERASE/INHIBITOR / SHMT2 / tetramer / glycine synthesis / inhibitor / TRANSFERASE / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


BRISC complex / L-allo-threonine aldolase activity / regulation of mitochondrial translation / L-serine metabolic process / glycine metabolic process / L-serine biosynthetic process / glycine hydroxymethyltransferase / glycine hydroxymethyltransferase activity / glycine biosynthetic process from serine / Metabolism of folate and pterines ...BRISC complex / L-allo-threonine aldolase activity / regulation of mitochondrial translation / L-serine metabolic process / glycine metabolic process / L-serine biosynthetic process / glycine hydroxymethyltransferase / glycine hydroxymethyltransferase activity / glycine biosynthetic process from serine / Metabolism of folate and pterines / regulation of oxidative phosphorylation / tetrahydrofolate metabolic process / response to type I interferon / protein K63-linked deubiquitination / tetrahydrofolate interconversion / regulation of aerobic respiration / amino acid binding / mitochondrial nucleoid / RHOG GTPase cycle / Mitochondrial protein degradation / protein tetramerization / microtubule cytoskeleton / pyridoxal phosphate binding / one-carbon metabolic process / protein homotetramerization / mitochondrial inner membrane / mitochondrial matrix / chromatin binding / positive regulation of cell population proliferation / mitochondrion / extracellular exosome / identical protein binding / nucleus / cytoplasm
Similarity search - Function
Serine hydroxymethyltransferase, pyridoxal phosphate binding site / Serine hydroxymethyltransferase pyridoxal-phosphate attachment site. / : / Serine hydroxymethyltransferase / Serine hydroxymethyltransferase-like domain / Serine hydroxymethyltransferase / Pyridoxal phosphate-dependent transferase, small domain / Pyridoxal phosphate-dependent transferase, major domain / Pyridoxal phosphate-dependent transferase
Similarity search - Domain/homology
GLYCINE / PYRIDOXAL-5'-PHOSPHATE / Chem-Y6U / Serine hydroxymethyltransferase, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.99 Å
AuthorsKatinas, J.M. / Dann III, C.E.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA250469 United States
CitationJournal: Biochemistry / Year: 2024
Title: Structural Characterization of 5-Substituted Pyrrolo[3,2- d ]pyrimidine Antifolate Inhibitors in Complex with Human Serine Hydroxymethyl Transferase 2.
Authors: Katinas, J.M. / Nayeen, M.J. / Schneider, M. / Shah, K. / Fifer, A.N. / Klapper, L.M. / Sharma, A. / Thalluri, K. / Van Nieuwenhze, M.S. / Hou, Z. / Gangjee, A. / Matherly, L.H. / Dann 3rd, C.E.
History
DepositionMar 20, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 20, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine hydroxymethyltransferase, mitochondrial
B: Serine hydroxymethyltransferase, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)110,7398
Polymers109,2122
Non-polymers1,5276
Water2,216123
1
A: Serine hydroxymethyltransferase, mitochondrial
hetero molecules

B: Serine hydroxymethyltransferase, mitochondrial
hetero molecules

B: Serine hydroxymethyltransferase, mitochondrial
hetero molecules

A: Serine hydroxymethyltransferase, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)221,47816
Polymers218,4244
Non-polymers3,05512
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z2
crystal symmetry operation12_564x,x-y+1,-z-1/62
Unit cell
Length a, b, c (Å)157.927, 157.927, 206.670
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number179
Space group name H-MP6522

-
Components

#1: Protein Serine hydroxymethyltransferase, mitochondrial / SHMT / Glycine hydroxymethyltransferase / Serine methylase


Mass: 54605.926 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SHMT2 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P34897, glycine hydroxymethyltransferase
#2: Chemical ChemComp-GLY / GLYCINE


Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H5NO2
#3: Chemical ChemComp-Y6U / N-{4-[3-(2-amino-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)propyl]benzoyl}-L-glutamic acid


Mass: 441.437 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H23N5O6 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-PLP / PYRIDOXAL-5'-PHOSPHATE / VITAMIN B6 Phosphate


Mass: 247.142 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H10NO6P
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 123 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.39 Å3/Da / Density % sol: 63.74 %
Crystal growTemperature: 277 K / Method: batch mode / pH: 7.5
Details: 20 mM sodium phosphate pH 7.5, 100 mM NaCl, 0.2 mM EDTA, and 0.5 mM TCEP and PLP loaded His-SHMT2 concentrated to 0.01 to 0.02 mM

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 4.2.2 / Wavelength: 1 Å
DetectorType: RDI CMOS_8M / Detector: CMOS / Date: Oct 8, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.99→48.5392 Å / Num. obs: 31441 / % possible obs: 100 % / Redundancy: 13.2 % / CC1/2: 0.928 / Rmerge(I) obs: 0.862 / Rpim(I) all: 0.245 / Rrim(I) all: 0.897 / Net I/σ(I): 4
Reflection shellResolution: 2.99→3.15 Å / Redundancy: 12.8 % / Rmerge(I) obs: 3.537 / Num. unique obs: 4485 / CC1/2: 0.313 / Rpim(I) all: 1.029 / Rrim(I) all: 3.686 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.13-2998refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.99→48.5392 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 26.95 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.274 1575 5.04 %
Rwork0.2227 --
obs0.2253 31223 99.47 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.99→48.5392 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7205 0 74 123 7402
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0027453
X-RAY DIFFRACTIONf_angle_d0.53710094
X-RAY DIFFRACTIONf_dihedral_angle_d3.3745345
X-RAY DIFFRACTIONf_chiral_restr0.0391099
X-RAY DIFFRACTIONf_plane_restr0.0041326
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.9901-3.0970.34411420.30482814X-RAY DIFFRACTION96
3.097-3.2210.30611250.29972905X-RAY DIFFRACTION99
3.221-3.36750.35921500.28132927X-RAY DIFFRACTION100
3.3675-3.5450.32721600.25522916X-RAY DIFFRACTION100
3.545-3.76710.31061620.23022955X-RAY DIFFRACTION100
3.7671-4.05780.24571650.19982945X-RAY DIFFRACTION100
4.0578-4.46590.24181760.19012937X-RAY DIFFRACTION100
4.4659-5.11150.24751500.18673010X-RAY DIFFRACTION100
5.1115-6.43760.26551550.21313037X-RAY DIFFRACTION100
6.4376-48.53920.27411470.21782761X-RAY DIFFRACTION100
6.6448-48.53920.22841900.19323202X-RAY DIFFRACTION100
Refinement TLS params.Method: refined / Origin x: -18.8505 Å / Origin y: 64.9575 Å / Origin z: 6.1869 Å
111213212223313233
T0.1144 Å2-0.0538 Å2-0.034 Å2-0.3374 Å2-0.0238 Å2--0.2175 Å2
L0.721 °20.311 °20.1494 °2-0.6832 °2-0.2119 °2--0.9555 °2
S-0.0119 Å °-0.0608 Å °0.015 Å °0.1029 Å °0.0098 Å °-0.1427 Å °-0.049 Å °0.3092 Å °-0.016 Å °
Refinement TLS groupSelection details: all

+
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