5M2K

Crystal structure of vancomycin-Zn(II) complex

PDB DOI: https://doi.org/10.2210/pdb5M2K/pdb

Classification: ANTIBIOTIC
Organism(s): Amycolatopsis orientalis
Mutation(s): No

Deposited: 2016-10-13 Released: 2017-07-19
Deposition Author(s): Zarkan, A., Macklyne, H.-R., Chirgadze, D.Y., Bond, A.D., Hesketh, A.R., Hong, H.-J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.00 Å
R-Value Free: 0.104
R-Value Work: 0.097
R-Value Observed: 0.098

wwPDB Validation 3D Report Full Report

This is version 4.0 of the entry. See complete history.

Literature

Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria.

Zarkan, A., Macklyne, H.R., Chirgadze, D.Y., Bond, A.D., Hesketh, A.R., Hong, H.J.

(2017) Sci Rep 7: 4893-4893

PubMed: 28687742 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41598-017-04868-2
Primary Citation of Related Structures:
5M2H, 5M2K

PubMed Abstract:
Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.

Organizational Affiliation

Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK.

Macromolecule Content

Total Structure Weight: 3.14 kDa
Atom Count: 274
Modelled Residue Count: 14
Deposited Residue Count: 14
Unique protein chains: 1

Macromolecules

Find similar proteins by: Sequence | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
vancomycin	A, B	7	Amycolatopsis orientalis	Mutation(s): 0
Glycosylation
Glycosylation Sites: 1	Glycosylation Focus chain A Focus chain B
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
vancosamine-(1-2)-beta-D-glucopyranose	C, D	2		N/A	Interactions Focus chain C Focus chain D Interactions & Density Focus chain C Focus chain D
Glycosylation Resources
GlyTouCan: G14263HU GlyCosmos: G14263HU

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain F [auth B] MOL2 format, chain F [auth B] mmCIF format, chain F [auth B]	F [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain F [auth B] Interactions & Density Focus chain F [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B]	E [auth A], G [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Interactions & Density Focus chain E [auth A] Focus chain G [auth B]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
OMY Query on OMY	A, B	L-PEPTIDE LINKING	C₉ H₁₀ Cl N O₄		TYR

Biologically Interesting Molecules (External Reference) 2 Unique

Entity ID: 1
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000204 Query on PRD_000204	A, B	Vancomycin	Glycopeptide / Antibiotic		Interactions Focus chain A Focus chain B Interactions & Density Focus chain A Focus chain B

Entity ID: 2
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000204 Query on PRD_000204	C, D	Vancomycin	Glycopeptide / Antibiotic		Interactions Focus chain C Focus chain D Interactions & Density Focus chain C Focus chain D

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.00 Å
R-Value Free: 0.104
R-Value Work: 0.097
R-Value Observed: 0.098
Space Group: H 3

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 35.899	α = 90
b = 35.899	β = 90
c = 55.553	γ = 120

Software Package:

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

Structure Validation

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Entry History

Deposition Data

Released Date: 2017-07-19

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2017-07-19
Type: Initial release
Version 2.0: 2018-06-13
Changes: Atomic model, Data collection, Database references, Structure summary
Version 3.0: 2019-04-24
Changes: Advisory, Data collection, Derived calculations, Polymer sequence
Version 3.1: 2019-07-10
Changes: Data collection
Version 4.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary