1zzt

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1zzt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zzt, resolution 2.14&Aring;" /> '''Bovine eNOS N368D/V1...)
Current revision (10:06, 20 December 2023) (edit) (undo)
 
(17 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1zzt.gif|left|200px]]<br /><applet load="1zzt" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1zzt, resolution 2.14&Aring;" />
 
-
'''Bovine eNOS N368D/V106M double mutant with L-N(omega)-Nitroarginine-(4R)-Amino-L-Proline Amide Bound'''<br />
 
-
==Overview==
+
==Bovine eNOS N368D/V106M double mutant with L-N(omega)-Nitroarginine-(4R)-Amino-L-Proline Amide Bound==
-
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.
+
<StructureSection load='1zzt' size='340' side='right'caption='[[1zzt]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1zzt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZZT FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=DP9:L-N(OMEGA)-NITROARGININE-(4R)-AMINO-L-PROLINE+AMIDE'>DP9</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=ZN:ZINC+ION'>ZN</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zzt OCA], [https://pdbe.org/1zzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zzt RCSB], [https://www.ebi.ac.uk/pdbsum/1zzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zzt ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zz/1zzt_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zzt ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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 Structure==
+
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<ref>PMID:16285725</ref>
-
1ZZT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ACT, ZN, HEM, H4B and DP9 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZZT OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16285725 16285725]
+
</div>
-
[[Category: Bos taurus]]
+
<div class="pdbe-citations 1zzt" style="background-color:#fffaf0;"></div>
-
[[Category: Nitric-oxide synthase]]
+
-
[[Category: Single protein]]
+
-
[[Category: Flinspach, M.L.]]
+
-
[[Category: Gomez-Vidal, J.A.]]
+
-
[[Category: Igarashi, J.]]
+
-
[[Category: Jamal, J.]]
+
-
[[Category: Li, H.]]
+
-
[[Category: Litzinger, E.A.]]
+
-
[[Category: Poulos, T.L.]]
+
-
[[Category: Silverman, R.B.]]
+
-
[[Category: Yang, W.]]
+
-
[[Category: ACT]]
+
-
[[Category: DP9]]
+
-
[[Category: H4B]]
+
-
[[Category: HEM]]
+
-
[[Category: ZN]]
+
-
[[Category: enzyme-inhibtor complex]]
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:45:49 2007''
+
==See Also==
 +
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Bos taurus]]
 +
[[Category: Large Structures]]
 +
[[Category: Flinspach ML]]
 +
[[Category: Gomez-Vidal JA]]
 +
[[Category: Igarashi J]]
 +
[[Category: Jamal J]]
 +
[[Category: Li H]]
 +
[[Category: Litzinger EA]]
 +
[[Category: Poulos TL]]
 +
[[Category: Silverman RB]]
 +
[[Category: Yang W]]

Current revision

Bovine eNOS N368D/V106M double mutant with L-N(omega)-Nitroarginine-(4R)-Amino-L-Proline Amide Bound

PDB ID 1zzt

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zzt"
Personal tools