9Q4X | pdb_00009q4x

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

PDB DOI: https://doi.org/10.2210/pdb9Q4X/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: 2.15 Å
R-Value Free:
0.261 (Depositor), 0.256 (DCC)
R-Value Work:
0.203 (Depositor), 0.200 (DCC)
R-Value Observed:
0.206 (Depositor)

Starting Model: experimental
View more details

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: 205.31 kDa
Atom Count: 13,841
Modeled Residue Count: 1,603
Deposited Residue Count: 1,760
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(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 IA [auth D] SDF format, chain P [auth B] SDF format, chain Y [auth C] MOL2 format, chain E [auth A] MOL2 format, chain IA [auth D] MOL2 format, chain P [auth B] MOL2 format, chain Y [auth C] mmCIF format, chain E [auth A] mmCIF format, chain IA [auth D] mmCIF format, chain P [auth B] mmCIF format, chain Y [auth C]	E [auth A], IA [auth D], P [auth B], Y [auth C]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain E [auth A] Focus chain IA [auth D] Focus chain P [auth B] Focus chain Y [auth C] Interactions & Density Focus chain E [auth A] Focus chain IA [auth D] Focus chain P [auth B] Focus chain Y [auth C]
A1CN2 (Subject of Investigation/LOI) Query on A1CN2 Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain G [auth A] SDF format, chain KA [auth D] SDF format, chain R [auth B] MOL2 format, chain AA [auth C] MOL2 format, chain G [auth A] MOL2 format, chain KA [auth D] MOL2 format, chain R [auth B] mmCIF format, chain AA [auth C] mmCIF format, chain G [auth A] mmCIF format, chain KA [auth D] mmCIF format, chain R [auth B]	AA [auth C], G [auth A], KA [auth D], R [auth B]	6-({5-[2-(dimethylamino)ethyl]-2,3-difluorophenoxy}methyl)-4-methylpyridin-2-amine C₁₇ H₂₁ F₂ N₃ O QWNQCAZGJZKYRU-UHFFFAOYSA-N		Interactions Focus chain AA [auth C] Focus chain G [auth A] Focus chain KA [auth D] Focus chain R [auth B] Interactions & Density Focus chain AA [auth C] Focus chain G [auth A] Focus chain KA [auth D] Focus chain R [auth B]
H4B Query on H4B Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain JA [auth D] SDF format, chain Q [auth B] SDF format, chain Z [auth C] MOL2 format, chain F [auth A] MOL2 format, chain JA [auth D] MOL2 format, chain Q [auth B] MOL2 format, chain Z [auth C] mmCIF format, chain F [auth A] mmCIF format, chain JA [auth D] mmCIF format, chain Q [auth B] mmCIF format, chain Z [auth C]	F [auth A], JA [auth D], Q [auth B], Z [auth C]	5,6,7,8-TETRAHYDROBIOPTERIN C₉ H₁₅ N₅ O₃ FNKQXYHWGSIFBK-RPDRRWSUSA-N		Interactions Focus chain F [auth A] Focus chain JA [auth D] Focus chain Q [auth B] Focus chain Z [auth C] Interactions & Density Focus chain F [auth A] Focus chain JA [auth D] Focus chain Q [auth B] Focus chain Z [auth C]
BTB Query on BTB Download Ideal Coordinates CCD File SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain LA [auth D] SDF format, chain MA [auth D] SDF format, chain S [auth B] SDF format, chain T [auth B] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain LA [auth D] MOL2 format, chain MA [auth D] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] mmCIF format, chain BA [auth C] mmCIF format, chain CA [auth C] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain LA [auth D] mmCIF format, chain MA [auth D] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B]	BA [auth C] CA [auth C] H [auth A] I [auth A] LA [auth D] BA [auth C], CA [auth C], H [auth A], I [auth A], LA [auth D], MA [auth D], S [auth B], T [auth B]	2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL C₈ H₁₉ N O₅ OWMVSZAMULFTJU-UHFFFAOYSA-N		Interactions Focus chain BA [auth C] Focus chain CA [auth C] Focus chain H [auth A] Focus chain I [auth A] Focus chain LA [auth D] Focus chain MA [auth D] Focus chain S [auth B] Focus chain T [auth B] Interactions & Density Focus chain BA [auth C] Focus chain CA [auth C] Focus chain H [auth A] Focus chain I [auth A] Focus chain LA [auth D] Focus chain MA [auth D] Focus chain S [auth B] Focus chain T [auth B]
GD Query on GD Download Ideal Coordinates CCD File SDF format, chain GA [auth C] SDF format, chain M [auth A] SDF format, chain PA [auth D] SDF format, chain W [auth B] MOL2 format, chain GA [auth C] MOL2 format, chain M [auth A] MOL2 format, chain PA [auth D] MOL2 format, chain W [auth B] mmCIF format, chain GA [auth C] mmCIF format, chain M [auth A] mmCIF format, chain PA [auth D] mmCIF format, chain W [auth B]	GA [auth C], M [auth A], PA [auth D], W [auth B]	GADOLINIUM ATOM Gd UIWYJDYFSGRHKR-UHFFFAOYSA-N		Interactions Focus chain GA [auth C] Focus chain M [auth A] Focus chain PA [auth D] Focus chain W [auth B] Interactions & Density Focus chain GA [auth C] Focus chain M [auth A] Focus chain PA [auth D] Focus chain W [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain DA [auth C] SDF format, chain EA [auth C] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain NA [auth D] SDF format, chain U [auth B] MOL2 format, chain DA [auth C] MOL2 format, chain EA [auth C] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain NA [auth D] MOL2 format, chain U [auth B] mmCIF format, chain DA [auth C] mmCIF format, chain EA [auth C] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain NA [auth D] mmCIF format, chain U [auth B]	DA [auth C] EA [auth C] J [auth A] K [auth A] NA [auth D] DA [auth C], EA [auth C], J [auth A], K [auth A], NA [auth D], U [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain DA [auth C] Focus chain EA [auth C] Focus chain J [auth A] Focus chain K [auth A] Focus chain NA [auth D] Focus chain U [auth B] Interactions & Density Focus chain DA [auth C] Focus chain EA [auth C] Focus chain J [auth A] Focus chain K [auth A] Focus chain NA [auth D] Focus chain U [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain HA [auth C] SDF format, chain N [auth A] MOL2 format, chain HA [auth C] MOL2 format, chain N [auth A] mmCIF format, chain HA [auth C] mmCIF format, chain N [auth A]	HA [auth C], N [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain HA [auth C] Focus chain N [auth A] Interactions & Density Focus chain HA [auth C] Focus chain N [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain O [auth A] SDF format, chain X [auth B] MOL2 format, chain O [auth A] MOL2 format, chain X [auth B] mmCIF format, chain O [auth A] mmCIF format, chain X [auth B]	O [auth A], X [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain O [auth A] Focus chain X [auth B] Interactions & Density Focus chain O [auth A] Focus chain X [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain FA [auth C] SDF format, chain L [auth A] SDF format, chain OA [auth D] SDF format, chain V [auth B] MOL2 format, chain FA [auth C] MOL2 format, chain L [auth A] MOL2 format, chain OA [auth D] MOL2 format, chain V [auth B] mmCIF format, chain FA [auth C] mmCIF format, chain L [auth A] mmCIF format, chain OA [auth D] mmCIF format, chain V [auth B]	FA [auth C], L [auth A], OA [auth D], V [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain FA [auth C] Focus chain L [auth A] Focus chain OA [auth D] Focus chain V [auth B] Interactions & Density Focus chain FA [auth C] Focus chain L [auth A] Focus chain OA [auth D] Focus chain V [auth B]