9Q58 | pdb_00009q58

Structure of human endothelial nitric oxide synthase heme domain bound with 6-((5-(2-(4,4-difluoropiperidin-1-yl)ethyl-2,3-difluorophenoxy)methyl)-4-methylpyridin-2-amine

PDB DOI: https://doi.org/10.2210/pdb9Q58/pdb

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

Deposited: 2025-08-20 Released: 2025-09-10
Deposition Author(s): Li, H., Poulos, T.L.
Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.03 Å
R-Value Free:
0.259 (Depositor), 0.255 (DCC)
R-Value Work:
0.205 (Depositor), 0.203 (DCC)
R-Value Observed:
0.208 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.0 of the entry. See complete history.

Literature

Highly potent, selective, and membrane permeable ether linked 2-aminopyridine-based human neuronal nitric oxide synthase inhibitors

Ansari, A., Chrzanowski, R.T., Li, H., Hardy, C.D., Poulos, T.L., Silverman, R.B.

To be published.

Macromolecule Content

Total Structure Weight: 205.48 kDa
Atom Count: 13,740
Modeled Residue Count: 1,604
Deposited Residue Count: 1,760
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Nitric oxide synthase 3	A, B, C, D	440	Homo sapiens	Mutation(s): 0 Gene Names: NOS3 EC: 1.14.13.39
UniProt & NIH Common Fund Data Resources
Find proteins for P29474 (Homo sapiens) Explore P29474 Go to UniProtKB: P29474
PHAROS: P29474 GTEx: ENSG00000164867
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P29474
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 9 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HEM Query on HEM Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain GA [auth D] SDF format, chain P [auth B] SDF format, chain W [auth C] MOL2 format, chain E [auth A] MOL2 format, chain GA [auth D] MOL2 format, chain P [auth B] MOL2 format, chain W [auth C] mmCIF format, chain E [auth A] mmCIF format, chain GA [auth D] mmCIF format, chain P [auth B] mmCIF format, chain W [auth C]	E [auth A], GA [auth D], P [auth B], W [auth C]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain E [auth A] Focus chain GA [auth D] Focus chain P [auth B] Focus chain W [auth C] Interactions & Density Focus chain E [auth A] Focus chain GA [auth D] Focus chain P [auth B] Focus chain W [auth C]
A1CN9 (Subject of Investigation/LOI) Query on A1CN9 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain IA [auth D] SDF format, chain R [auth B] SDF format, chain Y [auth C] MOL2 format, chain G [auth A] MOL2 format, chain IA [auth D] MOL2 format, chain R [auth B] MOL2 format, chain Y [auth C] mmCIF format, chain G [auth A] mmCIF format, chain IA [auth D] mmCIF format, chain R [auth B] mmCIF format, chain Y [auth C]	G [auth A], IA [auth D], R [auth B], Y [auth C]	6-({5-[2-(4,4-difluoropiperidin-1-yl)ethyl]-2,3-difluorophenoxy}methyl)-4-methylpyridin-2-amine C₂₀ H₂₃ F₄ N₃ O SCIIYAFRXFMLOP-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain IA [auth D] Focus chain R [auth B] Focus chain Y [auth C] Interactions & Density Focus chain G [auth A] Focus chain IA [auth D] Focus chain R [auth B] Focus chain Y [auth C]
H4B Query on H4B Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain HA [auth D] SDF format, chain Q [auth B] SDF format, chain X [auth C] MOL2 format, chain F [auth A] MOL2 format, chain HA [auth D] MOL2 format, chain Q [auth B] MOL2 format, chain X [auth C] mmCIF format, chain F [auth A] mmCIF format, chain HA [auth D] mmCIF format, chain Q [auth B] mmCIF format, chain X [auth C]	F [auth A], HA [auth D], Q [auth B], X [auth C]	5,6,7,8-TETRAHYDROBIOPTERIN C₉ H₁₅ N₅ O₃ FNKQXYHWGSIFBK-RPDRRWSUSA-N		Interactions Focus chain F [auth A] Focus chain HA [auth D] Focus chain Q [auth B] Focus chain X [auth C] Interactions & Density Focus chain F [auth A] Focus chain HA [auth D] Focus chain Q [auth B] Focus chain X [auth C]
BTB Query on BTB Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain JA [auth D] SDF format, chain KA [auth D] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain Z [auth C] MOL2 format, chain AA [auth C] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain JA [auth D] MOL2 format, chain KA [auth D] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain Z [auth C] mmCIF format, chain AA [auth C] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain JA [auth D] mmCIF format, chain KA [auth D] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B] mmCIF format, chain Z [auth C]	AA [auth C] H [auth A] I [auth A] JA [auth D] KA [auth D] AA [auth C], H [auth A], I [auth A], JA [auth D], KA [auth D], S [auth B], T [auth B], Z [auth C]	2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL C₈ H₁₉ N O₅ OWMVSZAMULFTJU-UHFFFAOYSA-N		Interactions Focus chain AA [auth C] Focus chain H [auth A] Focus chain I [auth A] Focus chain JA [auth D] Focus chain KA [auth D] Focus chain S [auth B] Focus chain T [auth B] Focus chain Z [auth C] Interactions & Density Focus chain AA [auth C] Focus chain H [auth A] Focus chain I [auth A] Focus chain JA [auth D] Focus chain KA [auth D] Focus chain S [auth B] Focus chain T [auth B] Focus chain Z [auth C]
GD Query on GD Download Ideal Coordinates CCD File SDF format, chain EA [auth C] SDF format, chain NA [auth D] SDF format, chain V [auth B] SDF format, chain M [auth A] MOL2 format, chain EA [auth C] MOL2 format, chain NA [auth D] MOL2 format, chain V [auth B] MOL2 format, chain M [auth A] mmCIF format, chain EA [auth C] mmCIF format, chain NA [auth D] mmCIF format, chain V [auth B] mmCIF format, chain M [auth A]	EA [auth C], M [auth A], NA [auth D], V [auth B]	GADOLINIUM ATOM Gd UIWYJDYFSGRHKR-UHFFFAOYSA-N		Interactions Focus chain EA [auth C] Focus chain M [auth A] Focus chain NA [auth D] Focus chain V [auth B] Interactions & Density Focus chain EA [auth C] Focus chain M [auth A] Focus chain NA [auth D] Focus chain V [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain LA [auth D] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain LA [auth D] mmCIF format, chain BA [auth C] mmCIF format, chain CA [auth C] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain LA [auth D]	BA [auth C], CA [auth C], J [auth A], K [auth A], LA [auth D]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain BA [auth C] Focus chain CA [auth C] Focus chain J [auth A] Focus chain K [auth A] Focus chain LA [auth D] Interactions & Density Focus chain BA [auth C] Focus chain CA [auth C] Focus chain J [auth A] Focus chain K [auth A] Focus chain LA [auth D]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain FA [auth C] SDF format, chain N [auth A] MOL2 format, chain FA [auth C] MOL2 format, chain N [auth A] mmCIF format, chain FA [auth C] mmCIF format, chain N [auth A]	FA [auth C], N [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain FA [auth C] Focus chain N [auth A] Interactions & Density Focus chain FA [auth C] Focus chain N [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain O [auth A] MOL2 format, chain O [auth A] mmCIF format, chain O [auth A]	O [auth A]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain O [auth A] Interactions & Density Focus chain O [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain DA [auth C] SDF format, chain L [auth A] SDF format, chain MA [auth D] SDF format, chain U [auth B] MOL2 format, chain DA [auth C] MOL2 format, chain L [auth A] MOL2 format, chain MA [auth D] MOL2 format, chain U [auth B] mmCIF format, chain DA [auth C] mmCIF format, chain L [auth A] mmCIF format, chain MA [auth D] mmCIF format, chain U [auth B]	DA [auth C], L [auth A], MA [auth D], U [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain DA [auth C] Focus chain L [auth A] Focus chain MA [auth D] Focus chain U [auth B] Interactions & Density Focus chain DA [auth C] Focus chain L [auth A] Focus chain MA [auth D] Focus chain U [auth B]