5WDJ

CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-6 AKA 7-(BENZYLOXY)-1H-[1,2, 3]TRIAZOLO[4,5-D]PYRIMIDIN-5-AMINE

PDB DOI: https://doi.org/10.2210/pdb5WDJ/pdb

Classification: METAL BINDING PROTEIN
Organism(s): Homo sapiens
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2017-07-05 Released: 2018-04-18
Deposition Author(s): Khan, J.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.248
R-Value Work: 0.194
R-Value Observed: 0.197

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 of the entry. See complete history.

Literature

Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.

Duclos, F., Abell, L.M., Harden, D.G., Pike, K., Nowak, K., Locke, G.A., Duke, G.J., Liu, X., Fernando, G., Shaw, S.A., Vokits, B.P., Wurtz, N.R., Viet, A., Valente, M.N., Stachura, S., Sleph, P., Khan, J.A., Gao, J., Dongre, A.R., Zhao, L., Wexler, R.R., Gordon, D.A., Kick, E.K.

(2017) Medchemcomm 8: 2093-2099

PubMed: 30108726 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/c7md00268h
Primary Citation of Related Structures:
5WDJ

PubMed Abstract:
Myeloperoxidase, a mammalian peroxidase involved in the immune system as an anti-microbial first responder, can produce hypochlorous acid in response to invading pathogens. Myeloperoxidase has been implicated in several chronic pathological diseases due to the chronic production of hypochlorous acid, as well as other reactive radical species. A high throughput screen and triaging protocol was developed to identify a reversible inhibitor of myeloperoxidase toward the potential treatment of chronic diseases such as atherosclerosis. The identification and characterization of a reversible myeloperoxidase inhibitor, 7-(benzyloxy)-3 H -[1,2,3]triazolo[4,5- d ]pyrimidin-5-amine is described.

Organizational Affiliation

Bristol-Myers Squibb Company , P.O. Box 5400 , Princeton , New Jersey 08543-5400 , USA . Email: [email protected].

Macromolecule Content

Total Structure Weight: 135.61 kDa
Atom Count: 9,895
Modelled Residue Count: 1,138
Deposited Residue Count: 1,144
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Myeloperoxidase	A, C [auth D]	105	Homo sapiens	Mutation(s): 0 Gene Names: MPO EC: 1.11.2.2
UniProt & NIH Common Fund Data Resources
Find proteins for P05164 (Homo sapiens) Explore P05164 Go to UniProtKB: P05164
PHAROS: P05164 GTEx: ENSG00000005381
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P05164
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Myeloperoxidase	B, D [auth E]	467	Homo sapiens	Mutation(s): 0 Gene Names: MPO EC: 1.11.2.2
UniProt & NIH Common Fund Data Resources
Find proteins for P05164 (Homo sapiens) Explore P05164 Go to UniProtKB: P05164
PHAROS: P05164 GTEx: ENSG00000005381
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P05164
Glycosylation
Glycosylation Sites: 3	Glycosylation Focus chain B Focus chain D [auth E]	Go to GlyGen: P05164-1
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	E [auth C]	3		N/A	Interactions Focus chain E [auth C] Interactions & Density Focus chain E [auth C]
Glycosylation Resources
GlyTouCan: G29301NP GlyCosmos: G29301NP GlyGen: G29301NP

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	F	3		N-Glycosylation	Interactions Focus chain F Interactions & Density Focus chain F
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Small Molecules

Ligands 7 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HEM Query on HEM Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain R [auth D] MOL2 format, chain I [auth A] MOL2 format, chain R [auth D] mmCIF format, chain I [auth A] mmCIF format, chain R [auth D]	I [auth A], R [auth D]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain I [auth A] Focus chain R [auth D] Interactions & Density Focus chain I [auth A] Focus chain R [auth D]
AEY Query on AEY Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain Y [auth E] MOL2 format, chain G [auth A] MOL2 format, chain Y [auth E] mmCIF format, chain G [auth A] mmCIF format, chain Y [auth E]	G [auth A], Y [auth E]	7-(benzyloxy)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine C₁₁ H₁₀ N₆ O ZHTBAYPUCDCQPX-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain Y [auth E] Interactions & Density Focus chain G [auth A] Focus chain Y [auth E]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain K [auth B] SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain W [auth E] SDF format, chain X [auth E] MOL2 format, chain K [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain W [auth E] MOL2 format, chain X [auth E] mmCIF format, chain K [auth B] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B] mmCIF format, chain W [auth E] mmCIF format, chain X [auth E]	K [auth B], M [auth B], N [auth B], W [auth E], X [auth E]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain K [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain W [auth E] Focus chain X [auth E] Interactions & Density Focus chain K [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain W [auth E] Focus chain X [auth E]
MAN Query on MAN Download Ideal Coordinates CCD File SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain U [auth E] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain U [auth E] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B] mmCIF format, chain U [auth E]	O [auth B], P [auth B], U [auth E]	alpha-D-mannopyranose C₆ H₁₂ O₆ WQZGKKKJIJFFOK-PQMKYFCFSA-N		Interactions Focus chain O [auth B] Focus chain P [auth B] Focus chain U [auth E] Interactions & Density Focus chain O [auth B] Focus chain P [auth B] Focus chain U [auth E]
FUC Query on FUC Download Ideal Coordinates CCD File SDF format, chain L [auth B] SDF format, chain V [auth E] MOL2 format, chain L [auth B] MOL2 format, chain V [auth E] mmCIF format, chain L [auth B] mmCIF format, chain V [auth E]	L [auth B], V [auth E]	alpha-L-fucopyranose C₆ H₁₂ O₅ SHZGCJCMOBCMKK-SXUWKVJYSA-N		Interactions Focus chain L [auth B] Focus chain V [auth E] Interactions & Density Focus chain L [auth B] Focus chain V [auth E]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain T [auth D] MOL2 format, chain J [auth A] MOL2 format, chain T [auth D] mmCIF format, chain J [auth A] mmCIF format, chain T [auth D]	J [auth A], T [auth D]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Focus chain T [auth D] Interactions & Density Focus chain J [auth A] Focus chain T [auth D]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain Q [auth B] SDF format, chain S [auth D] SDF format, chain Z [auth E] SDF format, chain H [auth A] MOL2 format, chain Q [auth B] MOL2 format, chain S [auth D] MOL2 format, chain Z [auth E] MOL2 format, chain H [auth A] mmCIF format, chain Q [auth B] mmCIF format, chain S [auth D] mmCIF format, chain Z [auth E] mmCIF format, chain H [auth A]	H [auth A], Q [auth B], S [auth D], Z [auth E]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain H [auth A] Focus chain Q [auth B] Focus chain S [auth D] Focus chain Z [auth E] Interactions & Density Focus chain H [auth A] Focus chain Q [auth B] Focus chain S [auth D] Focus chain Z [auth E]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
CSO Query on CSO	B, D [auth E]	L-PEPTIDE LINKING	C₃ H₇ N O₃ S		CYS

Binding Affinity Annotations
ID	Source	Binding Affinity
AEY	BindingDB: 5WDJ	IC50: min: 103, max: 110 (nM) from 3 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.248
R-Value Work: 0.194
R-Value Observed: 0.197
Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 103.925	α = 90
b = 103.925	β = 90
c = 242.276	γ = 90

Software Package:

Software Name	Purpose
BUSTER	refinement
PDB_EXTRACT	data extraction
HKL-2000	data reduction
SCALEPACK	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2018-04-18

Deposition Author(s):

Khan, J.A.

Revision History (Full details and data files)

Version 1.0: 2018-04-18
Type: Initial release
Version 1.1: 2018-10-31
Changes: Data collection, Database references
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2024-10-23
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary

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Help and Resources

5WDJ

CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-6 AKA 7-(BENZYLOXY)-1H-[1,2, 3]TRIAZOLO[4,5-D]PYRIMIDIN-5-AMINE

Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Entity ID: 2