1RS7

Rat neuronal NOS heme domain with D-phenylalanine-D-nitroarginine amide bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.216 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structures of the Neuronal and Endothelial Nitric Oxide Synthase Heme Domain with d-Nitroarginine-Containing Dipeptide Inhibitors Bound.

Flinspach, M.Li, H.Jamal, J.Yang, W.Huang, H.Silverman, R.B.Poulos, T.L.

(2004) Biochemistry 43: 5181-5187

  • DOI: https://doi.org/10.1021/bi0361867
  • Primary Citation of Related Structures:  
    1RS6, 1RS7, 1RS8, 1RS9

  • PubMed Abstract: 

    In a continuing effort to unravel the structural basis for isoform-selective inhibition of nitric oxide synthase (NOS) by various inhibitors, we have determined the crystal structures of the nNOS and eNOS heme domain bound with two D-nitroarginine-containing dipeptide inhibitors, D-Lys-D-Arg(NO)2-NH(2) and D-Phe-D-Arg(NO)2-NH(2). These two dipeptide inhibitors exhibit similar binding modes in the two constitutive NOS isozymes, which is consistent with the similar binding affinities for the two isoforms as determined by K(i) measurements. The D-nitroarginine-containing dipeptide inhibitors are not distinguished by the amino acid difference between nNOS and eNOS (Asp 597 and Asn 368, respectively) which is key in controlling isoform selection for nNOS over eNOS observed for the L-nitroarginine-containing dipeptide inhibitors reported previously [Flinspach, M., et al. (2004) Nat. Struct. Mol. Biol. 11, 54-59]. The lack of a free alpha-amino group on the D-nitroarginine moiety makes the dipeptide inhibitor steer away from the amino acid binding pocket near the active site. This allows the inhibitor to extend into the solvent-accessible channel farther away from the active site, which enables the inhibitors to explore new isoform-specific enzyme-inhibitor interactions. This might be the structural basis for why these D-nitroarginine-containing inhibitors are selective for nNOS (or eNOS) over iNOS.


  • Organizational Affiliation

    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nitric-oxide synthase, brain
A, B
421Rattus norvegicusMutation(s): 0 
Gene Names: brain
EC: 1.14.13.39
UniProt
Find proteins for P29476 (Rattus norvegicus)
Explore P29476 
Go to UniProtKB:  P29476
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29476
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEM
Query on HEM

Download Ideal Coordinates CCD File 
E [auth A],
J [auth B]
PROTOPORPHYRIN IX CONTAINING FE
C34 H32 Fe N4 O4
KABFMIBPWCXCRK-RGGAHWMASA-L
D7P
Query on D7P

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
D-PHENYLALANYL-N~5~-[(2,2-DIHYDROXYHYDRAZINO)(IMINO)METHYL]-D-ORNITHINAMIDE
C15 H25 N7 O4
XHGCEQHFMHULSW-VXGBXAGGSA-N
H4B
Query on H4B

Download Ideal Coordinates CCD File 
F [auth A],
K [auth B]
5,6,7,8-TETRAHYDROBIOPTERIN
C9 H15 N5 O3
FNKQXYHWGSIFBK-RPDRRWSUSA-N
MTL
Query on MTL

Download Ideal Coordinates CCD File 
H [auth B]D-MANNITOL
C6 H14 O6
FBPFZTCFMRRESA-KVTDHHQDSA-N
ZN
Query on ZN

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D [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
C [auth A],
I [auth B]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.085α = 90
b = 110.909β = 90
c = 165.032γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-18
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2011-09-21
    Changes: Non-polymer description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations