6XVG

Human Sirt6 3-318 in complex with ADP-ribose and the activator MDL-801

PDB DOI: https://doi.org/10.2210/pdb6XVG/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2020-01-22 Released: 2020-10-28
Deposition Author(s): You, W., Steegborn, C.
Funding Organization(s): German Research Foundation (DFG)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.230
R-Value Work: 0.204
R-Value Observed: 0.205

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Binding site for activator MDL-801 on SIRT6.

You, W., Steegborn, C.

(2021) Nat Chem Biol 17: 519-521

PubMed: 33649599 Search on PubMed
DOI: https://doi.org/10.1038/s41589-021-00749-y
Primary Citation of Related Structures:
6XUY, 6XV1, 6XV6, 6XVG

Organizational Affiliation

Department of Biochemistry, University of Bayreuth, Bayreuth, Germany.

Macromolecule Content

Total Structure Weight: 219.43 kDa
Atom Count: 13,647
Modelled Residue Count: 1,675
Deposited Residue Count: 1,896
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
NAD-dependent protein deacetylase sirtuin-6	A, B, C, D, E A, B, C, D, E, F	316	Homo sapiens	Mutation(s): 0 Gene Names: SIRT6, SIR2L6 EC: 2.3.1.286 (PDB Primary Data), 2.4.2 (UniProt), 2.3.1 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q8N6T7 (Homo sapiens) Explore Q8N6T7 Go to UniProtKB: Q8N6T7
PHAROS: Q8N6T7 GTEx: ENSG00000077463
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q8N6T7
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
8L9 (Subject of Investigation/LOI) Query on 8L9 Download Ideal Coordinates CCD File SDF format, chain EA [auth D] SDF format, chain J [auth A] SDF format, chain MA [auth E] SDF format, chain O [auth B] SDF format, chain SA [auth F] SDF format, chain Z [auth C] MOL2 format, chain EA [auth D] MOL2 format, chain J [auth A] MOL2 format, chain MA [auth E] MOL2 format, chain O [auth B] MOL2 format, chain SA [auth F] MOL2 format, chain Z [auth C] mmCIF format, chain EA [auth D] mmCIF format, chain J [auth A] mmCIF format, chain MA [auth E] mmCIF format, chain O [auth B] mmCIF format, chain SA [auth F] mmCIF format, chain Z [auth C]	EA [auth D] J [auth A] MA [auth E] O [auth B] SA [auth F] EA [auth D], J [auth A], MA [auth E], O [auth B], SA [auth F], Z [auth C]	5-[[3,5-bis(chloranyl)phenyl]sulfonylamino]-2-[(5-bromanyl-4-fluoranyl-2-methyl-phenyl)sulfamoyl]benzoic acid C₂₀ H₁₄ Br Cl₂ F N₂ O₆ S₂ MJYYUGUIBHEWRX-UHFFFAOYSA-N		Interactions Focus chain EA [auth D] Focus chain J [auth A] Focus chain MA [auth E] Focus chain O [auth B] Focus chain SA [auth F] Focus chain Z [auth C] Interactions & Density Focus chain EA [auth D] Focus chain J [auth A] Focus chain MA [auth E] Focus chain O [auth B] Focus chain SA [auth F] Focus chain Z [auth C]
AR6 Query on AR6 Download Ideal Coordinates CCD File SDF format, chain BA [auth D] SDF format, chain G [auth A] SDF format, chain JA [auth E] SDF format, chain L [auth B] SDF format, chain QA [auth F] SDF format, chain V [auth C] MOL2 format, chain BA [auth D] MOL2 format, chain G [auth A] MOL2 format, chain JA [auth E] MOL2 format, chain L [auth B] MOL2 format, chain QA [auth F] MOL2 format, chain V [auth C] mmCIF format, chain BA [auth D] mmCIF format, chain G [auth A] mmCIF format, chain JA [auth E] mmCIF format, chain L [auth B] mmCIF format, chain QA [auth F] mmCIF format, chain V [auth C]	BA [auth D] G [auth A] JA [auth E] L [auth B] QA [auth F] BA [auth D], G [auth A], JA [auth E], L [auth B], QA [auth F], V [auth C]	[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE C₁₅ H₂₃ N₅ O₁₄ P₂ SRNWOUGRCWSEMX-ZQSHOCFMSA-N		Interactions Focus chain BA [auth D] Focus chain G [auth A] Focus chain JA [auth E] Focus chain L [auth B] Focus chain QA [auth F] Focus chain V [auth C] Interactions & Density Focus chain BA [auth D] Focus chain G [auth A] Focus chain JA [auth E] Focus chain L [auth B] Focus chain QA [auth F] Focus chain V [auth C]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain FA [auth D] SDF format, chain GA [auth D] SDF format, chain HA [auth D] SDF format, chain K [auth A] SDF format, chain NA [auth E] SDF format, chain OA [auth E] SDF format, chain P [auth B] SDF format, chain PA [auth E] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] MOL2 format, chain AA [auth C] MOL2 format, chain FA [auth D] MOL2 format, chain GA [auth D] MOL2 format, chain HA [auth D] MOL2 format, chain K [auth A] MOL2 format, chain NA [auth E] MOL2 format, chain OA [auth E] MOL2 format, chain P [auth B] MOL2 format, chain PA [auth E] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] mmCIF format, chain AA [auth C] mmCIF format, chain FA [auth D] mmCIF format, chain GA [auth D] mmCIF format, chain HA [auth D] mmCIF format, chain K [auth A] mmCIF format, chain NA [auth E] mmCIF format, chain OA [auth E] mmCIF format, chain P [auth B] mmCIF format, chain PA [auth E] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B]	AA [auth C] FA [auth D] GA [auth D] HA [auth D] K [auth A] AA [auth C], FA [auth D], GA [auth D], HA [auth D], K [auth A], NA [auth E], OA [auth E], P [auth B], PA [auth E], Q [auth B], R [auth B], S [auth B], T [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AA [auth C] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain K [auth A] Focus chain NA [auth E] Focus chain OA [auth E] Focus chain P [auth B] Focus chain PA [auth E] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Interactions & Density Focus chain AA [auth C] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain K [auth A] Focus chain NA [auth E] Focus chain OA [auth E] Focus chain P [auth B] Focus chain PA [auth E] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain DA [auth D] SDF format, chain I [auth A] SDF format, chain IA [auth E] SDF format, chain LA [auth E] SDF format, chain N [auth B] SDF format, chain U [auth C] SDF format, chain X [auth C] SDF format, chain Y [auth C] MOL2 format, chain DA [auth D] MOL2 format, chain I [auth A] MOL2 format, chain IA [auth E] MOL2 format, chain LA [auth E] MOL2 format, chain N [auth B] MOL2 format, chain U [auth C] MOL2 format, chain X [auth C] MOL2 format, chain Y [auth C] mmCIF format, chain DA [auth D] mmCIF format, chain I [auth A] mmCIF format, chain IA [auth E] mmCIF format, chain LA [auth E] mmCIF format, chain N [auth B] mmCIF format, chain U [auth C] mmCIF format, chain X [auth C] mmCIF format, chain Y [auth C]	DA [auth D] I [auth A] IA [auth E] LA [auth E] N [auth B] DA [auth D], I [auth A], IA [auth E], LA [auth E], N [auth B], U [auth C], X [auth C], Y [auth C]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain DA [auth D] Focus chain I [auth A] Focus chain IA [auth E] Focus chain LA [auth E] Focus chain N [auth B] Focus chain U [auth C] Focus chain X [auth C] Focus chain Y [auth C] Interactions & Density Focus chain DA [auth D] Focus chain I [auth A] Focus chain IA [auth E] Focus chain LA [auth E] Focus chain N [auth B] Focus chain U [auth C] Focus chain X [auth C] Focus chain Y [auth C]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain CA [auth D] SDF format, chain H [auth A] SDF format, chain KA [auth E] SDF format, chain M [auth B] SDF format, chain RA [auth F] SDF format, chain W [auth C] MOL2 format, chain CA [auth D] MOL2 format, chain H [auth A] MOL2 format, chain KA [auth E] MOL2 format, chain M [auth B] MOL2 format, chain RA [auth F] MOL2 format, chain W [auth C] mmCIF format, chain CA [auth D] mmCIF format, chain H [auth A] mmCIF format, chain KA [auth E] mmCIF format, chain M [auth B] mmCIF format, chain RA [auth F] mmCIF format, chain W [auth C]	CA [auth D] H [auth A] KA [auth E] M [auth B] RA [auth F] CA [auth D], H [auth A], KA [auth E], M [auth B], RA [auth F], W [auth C]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain CA [auth D] Focus chain H [auth A] Focus chain KA [auth E] Focus chain M [auth B] Focus chain RA [auth F] Focus chain W [auth C] Interactions & Density Focus chain CA [auth D] Focus chain H [auth A] Focus chain KA [auth E] Focus chain M [auth B] Focus chain RA [auth F] Focus chain W [auth C]

Binding Affinity Annotations
ID	Source	Binding Affinity
8L9	BindingDB: 6XVG	EC50: min: 5700, max: 1.00e+4 (nM) from 2 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.230
R-Value Work: 0.204
R-Value Observed: 0.205
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 89.51	α = 90
b = 136.534	β = 117.71
c = 89.873	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XDS	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2020-10-28

Deposition Author(s):

You, W.

Steegborn, C.

Funding Organization	Location	Grant Number
German Research Foundation (DFG)	Germany	STE1701/15

Revision History (Full details and data files)

Version 1.0: 2020-10-28
Type: Initial release
Version 1.1: 2021-03-17
Changes: Database references
Version 1.2: 2021-05-05
Changes: Database references
Version 1.3: 2024-01-24
Changes: Data collection, Database references, Refinement description