4D0L

Phosphatidylinositol 4-kinase III beta-PIK93 in a complex with Rab11a- GTP gammaS

PDB DOI: https://doi.org/10.2210/pdb4D0L/pdb

Classification: TRANSFERASE/HYDROLASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda, Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2014-04-29 Released: 2014-05-28
Deposition Author(s): Burke, J.E., Inglis, A.J., Perisic, O., Masson, G.R., McLaughin, S.H., Rutaganira, F., Shokat, K.M., Williams, R.L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.94 ?
R-Value Free:
0.259 (Depositor), 0.260 (DCC)
R-Value Work:
0.216 (Depositor), 0.220 (DCC)
R-Value Observed:
0.218 (Depositor)

Starting Models: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Structures of Pi4Kiiibeta Complexes Show Simultaneous Recruitment of Rab11 and its Effectors.

Burke, J.E., Inglis, A.J., Perisic, O., Masson, G.R., Mclaughlin, S.H., Rutaganira, F., Shokat, K.M., Williams, R.L.

(2014) Science 344: 1035

PubMed: 24876499 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.1253397
Primary Citation of Related Structures:
4D0L, 4D0M

PubMed Abstract:
Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kβ (PI4KIIIβ) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIβ interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIβ coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.

Organizational Affiliation

Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk.

Macromolecule Content

Total Structure Weight: 270.72 kDa
Atom Count: 15,864
Modelled Residue Count: 1,952
Deposited Residue Count: 2,355
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PHOSPHATIDYLINOSITOL 4-KINASE BETA	A, C, E	566	Homo sapiens	Mutation(s): 1 EC: 2.7.1.67
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UBF8 (Homo sapiens) Explore Q9UBF8 Go to UniProtKB: Q9UBF8
PHAROS: Q9UBF8 GTEx: ENSG00000143393
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9UBF8
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
RAS-RELATED PROTEIN RAB-11A	B, D, F	219	Homo sapiens	Mutation(s): 1 EC: 3.6.5.2
UniProt & NIH Common Fund Data Resources
Find proteins for P62491 (Homo sapiens) Explore P62491 Go to UniProtKB: P62491
PHAROS: P62491 GTEx: ENSG00000103769
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P62491
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GSP Query on GSP Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain K [auth D] SDF format, chain N [auth F] MOL2 format, chain H [auth B] MOL2 format, chain K [auth D] MOL2 format, chain N [auth F] mmCIF format, chain H [auth B] mmCIF format, chain K [auth D] mmCIF format, chain N [auth F]	H [auth B], K [auth D], N [auth F]	5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE C₁₀ H₁₆ N₅ O₁₃ P₃ S XOFLBQFBSOEHOG-UUOKFMHZSA-N		Interactions Focus chain H [auth B] Focus chain K [auth D] Focus chain N [auth F] Interactions & Density Focus chain H [auth B] Focus chain K [auth D] Focus chain N [auth F]
093 Query on 093 Download Ideal Coordinates CCD File SDF format, chain J [auth C] SDF format, chain M [auth E] SDF format, chain G [auth A] MOL2 format, chain J [auth C] MOL2 format, chain M [auth E] MOL2 format, chain G [auth A] mmCIF format, chain J [auth C] mmCIF format, chain M [auth E] mmCIF format, chain G [auth A]	G [auth A], J [auth C], M [auth E]	N-(5-(4-CHLORO-3-(2-HYDROXY-ETHYLSULFAMOYL)- PHENYLTHIAZOLE-2-YL)-ACETAMIDE C₁₄ H₁₆ Cl N₃ O₄ S₂ JFVNFXCESCXMBC-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain J [auth C] Focus chain M [auth E] Interactions & Density Focus chain G [auth A] Focus chain J [auth C] Focus chain M [auth E]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain I [auth B] SDF format, chain L [auth D] SDF format, chain O [auth F] MOL2 format, chain I [auth B] MOL2 format, chain L [auth D] MOL2 format, chain O [auth F] mmCIF format, chain I [auth B] mmCIF format, chain L [auth D] mmCIF format, chain O [auth F]	I [auth B], L [auth D], O [auth F]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain I [auth B] Focus chain L [auth D] Focus chain O [auth F] Interactions & Density Focus chain I [auth B] Focus chain L [auth D] Focus chain O [auth F]

Binding Affinity Annotations
ID	Source	Binding Affinity
093	BindingDB: 4D0L	IC50: min: 19, max: 28 (nM) from 2 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.94 ?
R-Value Free: 0.259 (Depositor), 0.260 (DCC)
R-Value Work: 0.216 (Depositor), 0.220 (DCC)
R-Value Observed: 0.218 (Depositor)

Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 102.795	α = 90
b = 146.925	β = 90
c = 188.335	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-05-28

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-05-28
Type: Initial release
Version 1.1: 2014-06-11
Changes: Database references
Version 1.2: 2018-06-20
Changes: Advisory, Data collection, Derived calculations
Version 1.3: 2019-02-20
Changes: Advisory, Data collection, Derived calculations
Version 1.4: 2023-12-20
Changes: Advisory, Data collection, Database references, Derived calculations, Other, Refinement description