1dwx: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1dwx.gif|left|200px]]<br /><applet load="1dwx" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1dwx, resolution 2.60&Aring;" />
-'''MURINE INDUCIBLE NITRIC OXIDE SYNTHASE OXYGENASE DIMER N-HYDROXYARGININE AND TETRAHYDROBIOPTERIN'''<br />
-==Overview==
+==MURINE INDUCIBLE NITRIC OXIDE SYNTHASE OXYGENASE DIMER N-hydroxyarginine and tetrahydrobiopterin==
-The oxygenase domain of the inducible nitric oxide synthase (iNOSox;, residues 1-498) is a dimer that binds heme, L-arginine and, tetrahydrobiopterin (H(4)B) and is the site for nitric oxide synthesis. We, examined an N-terminal segment that contains a beta-hairpin hook, a zinc, ligation center and part of the H(4)B-binding site for its role in, dimerization, catalysis, and H(4)B and substrate interactions. Deletion, mutagenesis identified the minimum catalytic core and indicated that an, intact N-terminal beta-hairpin hook is essential. Alanine screening, mutagenesis of conserved residues in the hook revealed five positions, (K82, N83, D92, T93 and H95) where native properties were perturbed., Mutants fell into two classes: (i) incorrigible mutants that disrupt, side-chain hydrogen bonds and packing interactions with the iNOSox, C-terminus (N83, D92 and H95) and cause permanent defects in homodimer, formation, H(4)B binding and activity; and (ii) reformable mutants that, destabilize interactions of the residue main chain (K82 and T93) with the, C-terminus and cause similar defects that were reversible with high, concentrations of H(4)B. Heterodimers comprised of a hook-defective iNOSox, mutant subunit and a full-length iNOS subunit were active in almost all, cases. This suggests a mechanism whereby N-terminal hooks exchange between, subunits in solution to stabilize the dimer.
+<StructureSection load='1dwx' size='340' side='right'caption='[[1dwx]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1dwx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DWX 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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1dwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwx OCA], [https://pdbe.org/1dwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dwx RCSB], [https://www.ebi.ac.uk/pdbsum/1dwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwx ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
+== 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/dw/1dwx_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=1dwx ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nitric oxide synthases (NOSs) catalyze two mechanistically distinct, tetrahydrobiopterin (H(4)B)-dependent, heme-based oxidations that first convert L-arginine (L-Arg) to N(omega)-hydroxy-L-arginine (NHA) and then NHA to L-citrulline and nitric oxide. Structures of the murine inducible NOS oxygenase domain (iNOS(ox)) complexed with NHA indicate that NHA and L-Arg both bind with the same conformation adjacent to the heme iron and neither interacts directly with it nor with H(4)B. Steric restriction of dioxygen binding to the heme in the NHA complex suggests either small conformational adjustments in the ternary complex or a concerted reaction of dioxygen with NHA and the heme iron. Interactions of the NHA hydroxyl with active center beta-structure and the heme ring polarize and distort the hydroxyguanidinium to increase substrate reactivity. Steric constraints in the active center rule against superoxo-iron accepting a hydrogen atom from the NHA hydroxyl in their initial reaction, but support an Fe(III)-peroxo-NHA radical conjugate as an intermediate. However, our structures do not exclude an oxo-iron intermediate participating in either L-Arg or NHA oxidation. Identical binding modes for active H(4)B, the inactive quinonoid-dihydrobiopterin (q-H(2)B), and inactive 4-amino-H(4)B indicate that conformational differences cannot explain pterin inactivity. Different redox and/or protonation states of q-H(2)B and 4-amino-H(4)B relative to H(4)B likely affect their ability to electronically influence the heme and/or undergo redox reactions during NOS catalysis. On the basis of these structures, we propose a testable mechanism where neutral H(4)B transfers both an electron and a 3,4-amide proton to the heme during the first step of NO synthesis.
-==About this Structure==
+Structures of the N(omega)-hydroxy-L-arginine complex of inducible nitric oxide synthase oxygenase dimer with active and inactive pterins.,Crane BR, Arvai AS, Ghosh S, Getzoff ED, Stuehr DJ, Tainer JA Biochemistry. 2000 Apr 25;39(16):4608-21. PMID:10769116<ref>PMID:10769116</ref>
-DWX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4, HEM, H4B and HAR 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=1DWX OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook and pterin-binding segment in dimerization and tetrahydrobiopterin interaction., Ghosh DK, Crane BR, Ghosh S, Wolan D, Gachhui R, Crooks C, Presta A, Tainer JA, Getzoff ED, Stuehr DJ, EMBO J. 1999 Nov 15;18(22):6260-70. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10562538 10562538]
+</div>
+<div class="pdbe-citations 1dwx" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Nitric-oxide synthase]]
+[[Category: Arvai AS]]
-[[Category: Single protein]]
+[[Category: Crane BR]]
-[[Category: Arvai, A.S.]]
+[[Category: Getzoff ED]]
-[[Category: Crane, B.R.]]
+[[Category: Stuehr DJ]]
-[[Category: Getzoff, E.D.]]
+[[Category: Tainer JA]]
-[[Category: Stuehr, D.J.]]
-[[Category: Tainer, J.A.]]
-[[Category: H4B]]
-[[Category: HAR]]
-[[Category: HEM]]
-[[Category: SO4]]
-[[Category: dimer]]
-[[Category: h4b]]
-[[Category: heme]]
-[[Category: intermediate]]
-[[Category: nitric oxide monooxygenase]]
-[[Category: pterin]]
-[[Category: tetrahydrobiopterin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:38:56 2007''