1m00
From Proteopedia
(New page: 200px<br /><applet load="1m00" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m00, resolution 2.05Å" /> '''Rat neuronal NOS hem...) |
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| - | [[Image:1m00.gif|left|200px]]<br /><applet load="1m00" size=" | + | [[Image:1m00.gif|left|200px]]<br /><applet load="1m00" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1m00, resolution 2.05Å" /> | caption="1m00, resolution 2.05Å" /> | ||
'''Rat neuronal NOS heme domain with N-butyl-N'-hydroxyguanidine bound'''<br /> | '''Rat neuronal NOS heme domain with N-butyl-N'-hydroxyguanidine bound'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of N-alkyl-N'-hydroxyguanidine compounds have recently been | + | A series of N-alkyl-N'-hydroxyguanidine compounds have recently been characterized as non-amino acid substrates for all three nitric oxide synthase (NOS) isoforms which mimic NO formation from N(omega)-hydroxy-L-arginine. Crystal structures of the nNOS heme domain complexed with either N-isopropyl-N'-hydroxyguanidine or N-butyl-N'-hydroxyguanidine reveal two different binding modes in the substrate binding pocket. The binding mode of the latter is consistent with that observed for the substrate N(omega)-hydroxy-L-arginine bound in the nNOS active site. However, the former binds to nNOS in an unexpected fashion, thus providing new insights into the mechanism on how the hydroxyguanidine moiety leads to NO formation. Structural features of substrate binding support the view that the OH-substituted guanidine nitrogen, instead of the hydroxyl oxygen, is the source of hydrogen supplied to the active ferric-superoxy species for the second step of the NOS catalytic reaction. |
==About this Structure== | ==About this Structure== | ||
| - | 1M00 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ACT, ZN, HEM, H4B and BHH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http:// | + | 1M00 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=H4B:'>H4B</scene> and <scene name='pdbligand=BHH:'>BHH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M00 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Jia, Q.]] | [[Category: Jia, Q.]] | ||
[[Category: Li, H.]] | [[Category: Li, H.]] | ||
| - | [[Category: Poulos, T | + | [[Category: Poulos, T L.]] |
[[Category: Shimizu, H.]] | [[Category: Shimizu, H.]] | ||
| - | [[Category: Wang, P | + | [[Category: Wang, P G.]] |
| - | [[Category: Wen, E | + | [[Category: Wen, E Z.]] |
[[Category: Xian, M.]] | [[Category: Xian, M.]] | ||
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
| Line 34: | Line 34: | ||
[[Category: oxydoreductase]] | [[Category: oxydoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:50:04 2008'' |
Revision as of 11:50, 21 February 2008
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Rat neuronal NOS heme domain with N-butyl-N'-hydroxyguanidine bound
Overview
A series of N-alkyl-N'-hydroxyguanidine compounds have recently been characterized as non-amino acid substrates for all three nitric oxide synthase (NOS) isoforms which mimic NO formation from N(omega)-hydroxy-L-arginine. Crystal structures of the nNOS heme domain complexed with either N-isopropyl-N'-hydroxyguanidine or N-butyl-N'-hydroxyguanidine reveal two different binding modes in the substrate binding pocket. The binding mode of the latter is consistent with that observed for the substrate N(omega)-hydroxy-L-arginine bound in the nNOS active site. However, the former binds to nNOS in an unexpected fashion, thus providing new insights into the mechanism on how the hydroxyguanidine moiety leads to NO formation. Structural features of substrate binding support the view that the OH-substituted guanidine nitrogen, instead of the hydroxyl oxygen, is the source of hydrogen supplied to the active ferric-superoxy species for the second step of the NOS catalytic reaction.
About this Structure
1M00 is a Single protein structure of sequence from Rattus norvegicus with , , , and as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.
Reference
The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis., Li H, Shimizu H, Flinspach M, Jamal J, Yang W, Xian M, Cai T, Wen EZ, Jia Q, Wang PG, Poulos TL, Biochemistry. 2002 Nov 26;41(47):13868-75. PMID:12437343
Page seeded by OCA on Thu Feb 21 13:50:04 2008
Categories: Nitric-oxide synthase | Rattus norvegicus | Single protein | Cai, T. | Flinspach, M. | Jamal, J. | Jia, Q. | Li, H. | Poulos, T L. | Shimizu, H. | Wang, P G. | Wen, E Z. | Xian, M. | Yang, W. | ACT | BHH | H4B | HEM | ZN | Heme-enzyme | Nitric oxide synthase | Oxydoreductase
