8.A.24.2.4
Brain nitric oxide synthase, NOS1, of 1434 aas and probably 0 TMSs. It produces nitric oxide (NO) which is a messenger molecule with diverse
functions throughout the body. In the brain and peripheral nervous
system, NO displays many properties of a neurotransmitter. It probably has
nitrosylase activity and mediates cysteine S-nitrosylation of
cytoplasmic target proteins such SRR. Major depressive disorder (MDD) is one of the most common mental
disorders. Sun et al. 2022 designed a fast-onset antidepressant that works by
disrupting the interaction between the serotonin transporter (SERT; TC# 2.A.22.1.1) and
neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN).
Chronic unpredictable mild stress (CMS) selectively increases the
SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS
interactions in the DRN causes a depression-like phenotype and accounts
for CMS-induced depressive behaviors. Disrupting the SERT-nNOS
interaction produces a fast-onset antidepressant effect by enhancing
serotonin signaling in forebrain circuits. A
small-molecule compound, ZZL-7 elicits an antidepressant effect 2
hours after treatment without undesirable side effects. This compound,
or analogous reagents, may serve as a new, rapidly acting treatment for
MDD (Sun et al. 2022).
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| Accession Number: | P29475 |
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| Protein Name: | Nitric oxide synthase, brain |
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| Length: | 1434 |
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| Molecular Weight: | 160970.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Location1 / Topology2 / Orientation3: |
Cell membrane1 / Peripheral membrane protein2 |
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| Substrate |
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1: MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA
61: GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI
121: RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP
181: RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV
241: DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS
301: KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF
361: PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC
421: VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW
481: NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ
541: IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV
601: RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT
661: ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV
721: WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE
781: IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ
841: EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF
901: GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN
961: SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV
1021: RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV
1081: ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY
1141: EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPDMYP DEVHLTVAIV
1201: SYRTRDGEGP IHHGVCSSWL NRIQADELVP CFVRGAPSFH LPRNPQVPCI LVGPGTGIAP
1261: FRSFWQQRQF DIQHKGMNPC PMVLVFGCRQ SKIDHIYREE TLQAKNKGVF RELYTAYSRE
1321: PDKPKKYVQD ILQEQLAESV YRALKEQGGH IYVCGDVTMA ADVLKAIQRI MTQQGKLSAE
1381: DAGVFISRMR DDNRYHEDIF GVTLRTYEVT NRLRSESIAF IEESKKDTDE VFSS