4NEC

Conversion of a Disulfide Bond into a Thioacetal Group during Echinomycin Biosynthesis

PDB DOI: https://doi.org/10.2210/pdb4NEC/pdb

Classification: TRANSFERASE/ANTIBIOTIC
Organism(s): Streptomyces lasalocidi, Streptomyces echinatus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2013-10-29 Released: 2014-01-15
Deposition Author(s): Hotta, K., Keegan, R.M., Ranganathan, S., Fang, M., Bibby, J., Winn, M.D., Sato, M., Lian, M., Watanabe, K., Rigden, D.J., Kim, C.-Y.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.190
R-Value Work: 0.150
R-Value Observed: 0.152

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis.

Hotta, K., Keegan, R.M., Ranganathan, S., Fang, M., Bibby, J., Winn, M.D., Sato, M., Lian, M., Watanabe, K., Rigden, D.J., Kim, C.Y.

(2014) Angew Chem Int Ed Engl 53: 824-828

PubMed: 24302672 Search on PubMed
DOI: https://doi.org/10.1002/anie.201307404
Primary Citation of Related Structures:
4NEC

PubMed Abstract:
Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. It contains a thioacetal bridge, a unique chemical motif derived from the disulfide bond of its precursor antibiotic triostin A by the action of an S-adenosyl-L-methionine-dependent methyltransferase, Ecm18. The crystal structure of Ecm18 in complex with its reaction products S-adenosyl-L-homocysteine and echinomycin was determined at 1.50 Å resolution. Phasing was achieved using a new molecular replacement package called AMPLE, which automatically derives search models from structure predictions based on ab initio protein modelling. Structural analysis indicates that a combination of proximity effects, medium effects, and catalysis by strain drives the unique transformation of the disulfide bond into the thioacetal linkage.

Macromolecule Content

Total Structure Weight: 123.69 kDa
Atom Count: 8,028
Modelled Residue Count: 986
Deposited Residue Count: 1,088
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Putative SAM-dependent methyltransferase	A, C [auth B], E [auth C], G [auth D]	264	Streptomyces lasalocidi	Mutation(s): 0 Gene Names: ecm18
UniProt
Find proteins for Q0X0A7 (Streptomyces lasalocidi) Explore Q0X0A7 Go to UniProtKB: Q0X0A7
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q0X0A7
Sequence Annotations Expand
Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Echinomycin	B [auth E], D [auth F], F [auth G], H	8	Streptomyces echinatus	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 6 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
15P Query on 15P Download Ideal Coordinates CCD File SDF format, chain X [auth D] SDF format, chain Y [auth D] MOL2 format, chain X [auth D] MOL2 format, chain Y [auth D]	X [auth D], Y [auth D]	POLYETHYLENE GLYCOL (N=34) C₆₉ H₁₄₀ O₃₅ VUYXVWGKCKTUMF-UHFFFAOYSA-N		Interactions Focus chain X [auth D] Focus chain Y [auth D] Interactions & Density Focus chain X [auth D] Focus chain Y [auth D]
SAH Query on SAH Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain O [auth B] SDF format, chain S [auth C] SDF format, chain W [auth D] MOL2 format, chain I [auth A] MOL2 format, chain O [auth B] MOL2 format, chain S [auth C] MOL2 format, chain W [auth D]	I [auth A], O [auth B], S [auth C], W [auth D]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain I [auth A] Focus chain O [auth B] Focus chain S [auth C] Focus chain W [auth D] Interactions & Density Focus chain I [auth A] Focus chain O [auth B] Focus chain S [auth C] Focus chain W [auth D]
QUI Query on QUI Download Ideal Coordinates CCD File SDF format, chain AA [auth H] SDF format, chain BA [auth H] SDF format, chain M [auth E] SDF format, chain N [auth E] SDF format, chain Q [auth F] SDF format, chain R [auth F] SDF format, chain V [auth G] SDF format, chain U [auth G] MOL2 format, chain AA [auth H] MOL2 format, chain BA [auth H] MOL2 format, chain M [auth E] MOL2 format, chain N [auth E] MOL2 format, chain Q [auth F] MOL2 format, chain R [auth F] MOL2 format, chain V [auth G] MOL2 format, chain U [auth G]	AA [auth H] BA [auth H] M [auth E] N [auth E] Q [auth F] AA [auth H], BA [auth H], M [auth E], N [auth E], Q [auth F], R [auth F], U [auth G], V [auth G]	2-CARBOXYQUINOXALINE C₉ H₆ N₂ O₂ UPUZGXILYFKSGE-UHFFFAOYSA-N		Interactions Focus chain AA [auth H] Focus chain BA [auth H] Focus chain M [auth E] Focus chain N [auth E] Focus chain Q [auth F] Focus chain R [auth F] Focus chain U [auth G] Focus chain V [auth G] Interactions & Density Focus chain AA [auth H] Focus chain BA [auth H] Focus chain M [auth E] Focus chain N [auth E] Focus chain Q [auth F] Focus chain R [auth F] Focus chain U [auth G] Focus chain V [auth G]
PGE Query on PGE Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain Z [auth D] MOL2 format, chain J [auth A] MOL2 format, chain Z [auth D]	J [auth A], Z [auth D]	TRIETHYLENE GLYCOL C₆ H₁₄ O₄ ZIBGPFATKBEMQZ-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Focus chain Z [auth D] Interactions & Density Focus chain J [auth A] Focus chain Z [auth D]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain P [auth B] MOL2 format, chain P [auth B]	P [auth B]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain P [auth B] Interactions & Density Focus chain P [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain L [auth A] SDF format, chain T [auth C] SDF format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain T [auth C] MOL2 format, chain K [auth A]	K [auth A], L [auth A], T [auth C]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain K [auth A] Focus chain L [auth A] Focus chain T [auth C] Interactions & Density Focus chain K [auth A] Focus chain L [auth A] Focus chain T [auth C]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
MVA Query on MVA	B [auth E], D [auth F], F [auth G], H	L-PEPTIDE LINKING	C₆ H₁₃ N O₂		VAL

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 2
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000491 Query on PRD_000491	B [auth E], D [auth F], F [auth G], H	Echinomycin	Cyclic depsipeptide / Antibiotic		Interactions Focus chain B [auth E] Focus chain D [auth F] Focus chain F [auth G] Focus chain H Interactions & Density Focus chain B [auth E] Focus chain D [auth F] Focus chain F [auth G] Focus chain H

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.190
R-Value Work: 0.150
R-Value Observed: 0.152
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 58.187	α = 90
b = 146.88	β = 102.63
c = 58.187	γ = 90

Software Package:

Software Name	Purpose
MOSFLM	data reduction
AMPLE	phasing
REFMAC	refinement
Aimless	data scaling
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-01-15

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-01-15
Type: Initial release
Version 1.1: 2014-01-22
Changes: Structure summary
Version 1.2: 2022-08-24
Changes: Advisory, Database references, Derived calculations
Version 1.3: 2024-04-03
Changes: Data collection, Derived calculations, Refinement description

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Help and Resources

4NEC

Conversion of a Disulfide Bond into a Thioacetal Group during Echinomycin Biosynthesis

Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

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Entity ID: 2