4D1O

Structure of human endothelial nitric oxide synthase heme domain with L-Arg bound

Summary for 4D1O

• Entry DOI: 10.2210/pdb4d1o/pdb
• Related: 4D1N 4D1P
• Descriptor: NITRIC OXIDE SYNTHASE, ENDOTHELIAL, ARGININE, PROTOPORPHYRIN IX CONTAINING FE, ... (10 entities in total)
• Functional Keywords: oxidoreductase, nitric oxide synthase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell membrane: P29474
• Total number of polymer chains: 2
• Total formula weight: 102368.67

Authors

Li, H.,Poulos, T.L. (deposition date: 2014-05-02, release date: 2014-10-15, Last modification date: 2023-12-20)

Primary citation

Li, H.,Jamal, J.,Plaza, C.,Pineda, S.H.,Chreifi, G.,Jing, Q.,Cinelli, M.A.,Silverman, R.B.,Poulos, T.L.
Structures of Human Constitutive Nitric Oxide Synthases
Acta Crystallogr.,Sect.D, 70:2667-, 2014

PubMed 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 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution.

PubMed: 25286850
DOI: 10.1107/S1399004714017064

Experimental method

X-RAY DIFFRACTION (1.819 Å)