1zzr: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1zzr.gif|left|200px]] | [[Image:1zzr.gif|left|200px]] | ||
'''Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound''' | {{Structure | ||
|PDB= 1zzr |SIZE=350|CAPTION= <scene name='initialview01'>1zzr</scene>, resolution 2.05Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=DP9:L-N(OMEGA)-NITROARGININE-(4R)-AMINO-L-PROLINE+AMIDE'>DP9</scene>, <scene name='pdbligand=TFA:TRIFLUOROACETYL+GROUP'>TFA</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [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] | |||
|GENE= Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |||
}} | |||
'''Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1ZZR is a [ | 1ZZR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZZR OCA]. | ||
==Reference== | ==Reference== | ||
Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases., Li H, Flinspach ML, Igarashi J, Jamal J, Yang W, Gomez-Vidal JA, Litzinger EA, Huang H, Erdal EP, Silverman RB, Poulos TL, Biochemistry. 2005 Nov 22;44(46):15222-9. PMID:[http:// | Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases., Li H, Flinspach ML, Igarashi J, Jamal J, Yang W, Gomez-Vidal JA, Litzinger EA, Huang H, Erdal EP, Silverman RB, Poulos TL, Biochemistry. 2005 Nov 22;44(46):15222-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16285725 16285725] | ||
[[Category: Nitric-oxide synthase]] | [[Category: Nitric-oxide synthase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| Line 31: | Line 40: | ||
[[Category: oxydoreductase enzyme-inhibtor complex]] | [[Category: oxydoreductase enzyme-inhibtor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:41:47 2008'' | ||
Revision as of 16:41, 20 March 2008
| |||||||
| , resolution 2.05Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , and | ||||||
| Gene: | Nos1, Bnos (Rattus norvegicus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound
OverviewOverview
A series of L-nitroarginine-based dipeptide inhibitors are highly selective for neuronal nitric oxide synthase (nNOS) over the endothelial isoform (eNOS). Crystal structures of these dipeptides bound to both isoforms revealed two different conformations, curled in nNOS and extended in eNOS, corresponding to higher and lower binding affinity to the two isoforms, respectively. In previous studies we found that the primary reason for selectivity is that Asp597 in nNOS, which is Asn368 in eNOS, provides greater electrostatic stabilization in the inhibitor complex. While this is the case for smaller dipeptide inhibitors, electrostatic stabilization may no longer be the sole determinant for isoform selectivity with bulkier dipeptide inhibitors. Another residue farther away from the active site, Met336 in nNOS (Val106 in eNOS), is in contact with bulkier dipeptide inhibitors. Double mutants were made to exchange the D597/M336 pair in nNOS with N368/V106 in eNOS. Here we report crystal structures and inhibition constants for bulkier dipeptide inhibitors bound to nNOS and eNOS that illustrate the important role played by residues near the entry to the active site in isoform selective inhibition.
About this StructureAbout this Structure
1ZZR is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases., Li H, Flinspach ML, Igarashi J, Jamal J, Yang W, Gomez-Vidal JA, Litzinger EA, Huang H, Erdal EP, Silverman RB, Poulos TL, Biochemistry. 2005 Nov 22;44(46):15222-9. PMID:16285725
Page seeded by OCA on Thu Mar 20 15:41:47 2008