6R1M

Crystal structure of E. coli seryl-tRNA synthetase complexed to seryl sulfamoyl adenosine

PDB DOI: https://doi.org/10.2210/pdb6R1M/pdb

Classification: LIGASE
Organism(s): Escherichia coli
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2019-03-14 Released: 2020-01-22
Deposition Author(s): Salimraj, R., Cain, R., Roper, D.I.
Funding Organization(s): Medical Research Council (United Kingdom)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.180
R-Value Work: 0.162
R-Value Observed: 0.163

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.

Cain, R., Salimraj, R., Punekar, A.S., Bellini, D., Fishwick, C.W.G., Czaplewski, L., Scott, D.J., Harris, G., Dowson, C.G., Lloyd, A.J., Roper, D.I.

(2019) J Med Chem 62: 9703-9717

PubMed: 31626547 Search on PubMed
DOI: https://doi.org/10.1021/acs.jmedchem.9b01131
Primary Citation of Related Structures:
6R1M, 6R1N, 6R1O

PubMed Abstract:
Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the Escherichia coli and Staphylococcus aureus seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.

Organizational Affiliation

School of Life Sciences , University of Warwick , Gibbet Hill Road , Coventry CV4 7AL , United Kingdom.

Macromolecule Content

Total Structure Weight: 100.82 kDa
Atom Count: 7,889
Modelled Residue Count: 858
Deposited Residue Count: 874
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Serine--tRNA ligase	A, B	437	Escherichia coli	Mutation(s): 0 Gene Names: serS, ECVG_02257 EC: 6.1.1.11
UniProt
Find proteins for P0A8L1 (Escherichia coli (strain K12)) Explore P0A8L1 Go to UniProtKB: P0A8L1
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0A8L1
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SSA (Subject of Investigation/LOI) Query on SSA Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain N [auth B] MOL2 format, chain C [auth A] MOL2 format, chain N [auth B] mmCIF format, chain C [auth A] mmCIF format, chain N [auth B]	C [auth A], N [auth B]	5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE C₁₃ H₁₉ N₇ O₈ S HQXFJGONGJPTLZ-YTMOPEAISA-N		Interactions Focus chain C [auth A] Focus chain N [auth B] Interactions & Density Focus chain C [auth A] Focus chain N [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain Q [auth B] MOL2 format, chain D [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] mmCIF format, chain D [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B]	D [auth A], O [auth B], P [auth B], Q [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain D [auth A] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Interactions & Density Focus chain D [auth A] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] SDF format, chain Y [auth B] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] MOL2 format, chain Y [auth B] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B] mmCIF format, chain V [auth B] mmCIF format, chain W [auth B] mmCIF format, chain X [auth B] mmCIF format, chain Y [auth B]	E [auth A] F [auth A] G [auth A] H [auth A] I [auth A] E [auth A], F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], R [auth B], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth B], Y [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
SSA	BindingDB: 6R1M	Ki: 0.18 (nM) from 1 assay(s)
		Kd: 1.3 (nM) from 1 assay(s)
		IC50: 210 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.180
R-Value Work: 0.162
R-Value Observed: 0.163
Space Group: P 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 63.07	α = 75.44
b = 63.52	β = 70.25
c = 75.89	γ = 89.2

Software Package:

Software Name	Purpose
BUSTER	refinement
iMOSFLM	data reduction
Aimless	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2020-01-22

Deposition Author(s):

Salimraj, R.

Cain, R.

Roper, D.I.

Funding Organization	Location	Grant Number
Medical Research Council (United Kingdom)	United Kingdom	MR/M017893/1

Revision History (Full details and data files)

Version 1.0: 2020-01-22
Type: Initial release
Version 1.1: 2024-01-24
Changes: Data collection, Database references, Refinement description

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Help and Resources

6R1M

Crystal structure of E. coli seryl-tRNA synthetase complexed to seryl sulfamoyl adenosine

Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)