4D1O: Structure Of Human Endothelial Nitric Oxide Synthase Heme Domain With L-arg Bound

Citation:
Abstract
Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 A resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 A resolution.
PDB ID: 4D1ODownload
MMDB ID: 123778
PDB Deposition Date: 2014/5/2
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 1.82  Å
Source Organism:
Similar Structures:
Biological Unit for 4D1O: dimeric; determined by author and by software (PISA)
Molecular Components in 4D1O
Label Count Molecule
Proteins (2 molecules)
2
Nitric Oxide Synthase, Endothelial(Gene symbol: NOS3)
Molecule annotation
Chemicals (18 molecules)
1
2
2
2
3
2
4
4
5
3
6
1
7
2
8
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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