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==Structure of Bacillus subtilis Nitric Oxide Synthase in complex with 6-(5-((3R,4R)-4-((6-azanyl-4-methyl-pyridin-2-yl)methyl)pyrrolidin-3- yl)oxypentyl)-4-methyl-pyridin-2-amine== | ==Structure of Bacillus subtilis Nitric Oxide Synthase in complex with 6-(5-((3R,4R)-4-((6-azanyl-4-methyl-pyridin-2-yl)methyl)pyrrolidin-3- yl)oxypentyl)-4-methyl-pyridin-2-amine== | ||
<StructureSection load='4ug8' size='340' side='right' caption='[[4ug8]], [[Resolution|resolution]] 1.89Å' scene=''> | <StructureSection load='4ug8' size='340' side='right'caption='[[4ug8]], [[Resolution|resolution]] 1.89Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ug8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacsu Bacsu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UG8 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[4ug8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacsu Bacsu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UG8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4UG8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HW1:6-[5-({(3R,4R)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}OXY)PENTYL]-4-METHYLPYRIDIN-2-AMINE'>HW1</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HW1:6-[5-({(3R,4R)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}OXY)PENTYL]-4-METHYLPYRIDIN-2-AMINE'>HW1</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ug5|4ug5]], [[4ug6|4ug6]], [[4ug7|4ug7]], [[4ug9|4ug9]], [[4uga|4uga]], [[4ugb|4ugb]], [[4ugc|4ugc]], [[4ugd|4ugd]], [[4uge|4uge]], [[4ugf|4ugf]], [[4ugg|4ugg]], [[4ugh|4ugh]], [[4ugi|4ugi]], [[4ugj|4ugj]], [[4ugk|4ugk]], [[4ugl|4ugl]], [[4ugm|4ugm]], [[4ugn|4ugn]], [[4ugo|4ugo]], [[4ugp|4ugp]], [[4ugq|4ugq]], [[4ugr|4ugr]], [[4ugs|4ugs]], [[4ugt|4ugt]], [[4ugu|4ugu]], [[4ugv|4ugv]], [[4ugw|4ugw]], [[4ugx|4ugx]], [[4ugy|4ugy]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ug5|4ug5]], [[4ug6|4ug6]], [[4ug7|4ug7]], [[4ug9|4ug9]], [[4uga|4uga]], [[4ugb|4ugb]], [[4ugc|4ugc]], [[4ugd|4ugd]], [[4uge|4uge]], [[4ugf|4ugf]], [[4ugg|4ugg]], [[4ugh|4ugh]], [[4ugi|4ugi]], [[4ugj|4ugj]], [[4ugk|4ugk]], [[4ugl|4ugl]], [[4ugm|4ugm]], [[4ugn|4ugn]], [[4ugo|4ugo]], [[4ugp|4ugp]], [[4ugq|4ugq]], [[4ugr|4ugr]], [[4ugs|4ugs]], [[4ugt|4ugt]], [[4ugu|4ugu]], [[4ugv|4ugv]], [[4ugw|4ugw]], [[4ugx|4ugx]], [[4ugy|4ugy]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NAD(P)H-dependent) Nitric-oxide synthase (NAD(P)H-dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.165 1.14.13.165] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NAD(P)H-dependent) Nitric-oxide synthase (NAD(P)H-dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.165 1.14.13.165] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4ug8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ug8 OCA], [http://pdbe.org/4ug8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ug8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ug8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ug8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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==See Also== | ==See Also== | ||
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]] | *[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 28: | Line 28: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacsu]] | [[Category: Bacsu]] | ||
[[Category: Large Structures]] | |||
[[Category: Holden, J K]] | [[Category: Holden, J K]] | ||
[[Category: Poulos, T L]] | [[Category: Poulos, T L]] | ||
Revision as of 11:20, 4 November 2020
Structure of Bacillus subtilis Nitric Oxide Synthase in complex with 6-(5-((3R,4R)-4-((6-azanyl-4-methyl-pyridin-2-yl)methyl)pyrrolidin-3- yl)oxypentyl)-4-methyl-pyridin-2-amineStructure of Bacillus subtilis Nitric Oxide Synthase in complex with 6-(5-((3R,4R)-4-((6-azanyl-4-methyl-pyridin-2-yl)methyl)pyrrolidin-3- yl)oxypentyl)-4-methyl-pyridin-2-amine
Structural highlights
Function[NOSO_BACSU] Catalyzes the production of nitric oxide. Publication Abstract from PubMedNitric oxide generated by bacterial nitric oxide synthase (NOS) increases the susceptibility of Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. Not surprisingly, NOS inhibitors also improve the effectiveness of antimicrobials. Development of potent and selective bacterial NOS inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian NOS isoforms. To exploit bacterial NOS for the development of new therapeutics, recognition of alternative NOS surfaces and pharmacophores suitable for drug binding is required. Here, we report on a wide number of inhibitor-bound bacterial NOS crystal structures to identify several compounds that interact with surfaces unique to the bacterial NOS. Although binding studies indicate that these inhibitors weakly interact with the NOS active site, many of the inhibitors reported here provide a revised structural framework for the development of new antimicrobials that target bacterial NOS. In addition, mutagenesis studies reveal several key residues that unlock access to bacterial NOS surfaces that could provide the selectivity required to develop potent bacterial NOS inhibitors. Inhibitor Bound Crystal Structures of Bacterial Nitric Oxide Synthase.,Holden JK, Dejam D, Lewis MC, Huang H, Kang S, Jing Q, Xue F, Silverman RB, Poulos TL Biochemistry. 2015 Jun 23. PMID:26062720[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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