6B6U

Pyruvate Kinase M2 mutant - S437Y

PDB DOI: https://doi.org/10.2210/pdb6B6U/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2017-10-03 Released: 2017-12-20
Deposition Author(s): Srivastava, D., Dey, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.35 ?
R-Value Free: 0.149
R-Value Work: 0.130
R-Value Observed: 0.131

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.2 of the entry. See complete history.

Literature

Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform 2.

Srivastava, D., Razzaghi, M., Henzl, M.T., Dey, M.

(2017) Biochemistry 56: 6517-6520

PubMed: 29182273 Search on PubMed
DOI: https://doi.org/10.1021/acs.biochem.7b01013
Primary Citation of Related Structures:
6B6U

PubMed Abstract:
Pyruvate kinase muscle isoform 2 (PKM2) catalyzes the terminal step in glycolysis, transferring a phosphoryl group from phosphoenolpyruvate to ADP, to produce pyruvate and ATP. PKM2 activity is allosterically regulated by fructose 1,6-bisphosphate (FBP), an upstream glycolytic intermediate. FBP stabilizes the tetrameric form of the enzyme. In its absence, the PKM2 tetramers dissociate, yielding a dimer-monomer mixture having lower enzymatic activity. The S437Y variant of PKM2 is incapable of binding FBP. Consistent with that defect, we find that S437Y exists in a monomer-dimer equilibrium in solution, with a K _d of ～20 μM. Interestingly, however, the protein crystallizes as a tetramer, providing insight into the structural basis for impaired FBP binding of S437Y.

Organizational Affiliation

Department of Chemistry, University of Iowa , Iowa City, Iowa 52242, United States.

Macromolecule Content

Total Structure Weight: 116.5 kDa
Atom Count: 9,239
Modelled Residue Count: 1,041
Deposited Residue Count: 1,050
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Pyruvate kinase PKM	A, B	525	Homo sapiens	Mutation(s): 1 Gene Names: PKM, OIP3, PK2, PK3, PKM2 EC: 2.7.1.40 (PDB Primary Data), 2.7.11.1 (UniProt), 2.7.10.2 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P14618 (Homo sapiens) Explore P14618 Go to UniProtKB: P14618
PHAROS: P14618 GTEx: ENSG00000067225
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P14618
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 9 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
B3P Query on B3P Download Ideal Coordinates CCD File SDF format, chain K [auth A] SDF format, chain U [auth B] MOL2 format, chain K [auth A] MOL2 format, chain U [auth B] mmCIF format, chain K [auth A] mmCIF format, chain U [auth B]	K [auth A], U [auth B]	2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL C₁₁ H₂₆ N₂ O₆ HHKZCCWKTZRCCL-UHFFFAOYSA-N		Interactions Focus chain K [auth A] Focus chain U [auth B] Interactions & Density Focus chain K [auth A] Focus chain U [auth B]
PG4 Query on PG4 Download Ideal Coordinates CCD File SDF format, chain S [auth B] MOL2 format, chain S [auth B] mmCIF format, chain S [auth B]	S [auth B]	TETRAETHYLENE GLYCOL C₈ H₁₈ O₅ UWHCKJMYHZGTIT-UHFFFAOYSA-N		Interactions Focus chain S [auth B] Interactions & Density Focus chain S [auth B]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain J [auth A] MOL2 format, chain J [auth A] mmCIF format, chain J [auth A]	J [auth A]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]
OXL Query on OXL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain M [auth B] MOL2 format, chain D [auth A] MOL2 format, chain M [auth B] mmCIF format, chain D [auth A] mmCIF format, chain M [auth B]	D [auth A], M [auth B]	OXALATE ION C₂ O₄ MUBZPKHOEPUJKR-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain M [auth B] Interactions & Density Focus chain D [auth A] Focus chain M [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain T [auth B] MOL2 format, chain T [auth B] mmCIF format, chain T [auth B]	T [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain T [auth B] Interactions & Density Focus chain T [auth B]
SCN Query on SCN Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth B]	G [auth A] H [auth A] I [auth A] P [auth B] Q [auth B] G [auth A], H [auth A], I [auth A], P [auth B], Q [auth B], R [auth B]	THIOCYANATE ION C N S ZMZDMBWJUHKJPS-UHFFFAOYSA-M		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B]
K Query on K Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain N [auth B] MOL2 format, chain E [auth A] MOL2 format, chain N [auth B] mmCIF format, chain E [auth A] mmCIF format, chain N [auth B]	E [auth A], N [auth B]	POTASSIUM ION K NPYPAHLBTDXSSS-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain N [auth B] Interactions & Density Focus chain E [auth A] Focus chain N [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain O [auth B] MOL2 format, chain F [auth A] MOL2 format, chain O [auth B] mmCIF format, chain F [auth A] mmCIF format, chain O [auth B]	F [auth A], O [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain F [auth A] Focus chain O [auth B] Interactions & Density Focus chain F [auth A] Focus chain O [auth B]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain L [auth B] MOL2 format, chain C [auth A] MOL2 format, chain L [auth B] mmCIF format, chain C [auth A] mmCIF format, chain L [auth B]	C [auth A], L [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain L [auth B] Interactions & Density Focus chain C [auth A] Focus chain L [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.35 ?
R-Value Free: 0.149
R-Value Work: 0.130
R-Value Observed: 0.131
Space Group: C 1 2 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 110.35	α = 90
b = 93.61	β = 95.64
c = 109.36	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
SCALA	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction
XDS	data processing
Coot	model building

Structure Validation

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Entry History

Deposition Data

Released Date: 2017-12-20

Deposition Author(s):

Srivastava, D.

Dey, M.

Revision History (Full details and data files)

Version 1.0: 2017-12-20
Type: Initial release
Version 1.1: 2018-01-03
Changes: Database references
Version 1.2: 2023-10-04
Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description

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Help and Resources

6B6U

Pyruvate Kinase M2 mutant - S437Y

Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform 2.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Deposition Data

Revision History (Full details and data files)