2ci5

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:14, 6 March 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2ci5.gif|left|200px]]<br /><applet load="2ci5" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2ci5, resolution 1.79&Aring;" />
 
-
'''CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I IN COMPLEX WITH L-HOMOCYSTEINE'''<br />
 
-
==Overview==
+
==Crystal structure of Dimethylarginine Dimethylaminohydrolase I in complex with L-homocysteine==
-
Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the regulation of nitric oxide synthase (NOS) by metabolizing the free endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive inhibitors of NOS. Here, we present high-resolution crystal structures of DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a regulator of this mammalian enzyme. The structure of DDAH-1 consists of a propeller-like fold similar to other arginine-modifying enzymes and a flexible loop, which adopts different conformations and acts as a lid at the entrance of the active site. The orientation and interaction mode of inhibitors in the active site give insight into the regulation and the molecular mechanism of the enzyme. The presented structures provide a basis for the structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases.
+
<StructureSection load='2ci5' size='340' side='right'caption='[[2ci5]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
-
 
+
== Structural highlights ==
-
==About this Structure==
+
<table><tr><td colspan='2'>[[2ci5]] 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=2CI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CI5 FirstGlance]. <br>
-
2CI5 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 <scene name='pdbligand=HCS:'>HCS</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dimethylargininase Dimethylargininase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.18 3.5.3.18] Known structural/functional Site: <scene name='pdbsite=AC1:Cit+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CI5 OCA].
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
-
 
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=HCS:2-AMINO-4-MERCAPTO-BUTYRIC+ACID'>HCS</scene></td></tr>
-
==Reference==
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ci5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ci5 OCA], [https://pdbe.org/2ci5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ci5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ci5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ci5 ProSAT]</span></td></tr>
-
Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors., Frey D, Braun O, Briand C, Vasak M, Grutter MG, Structure. 2006 May;14(5):901-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16698551 16698551]
+
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/DDAH1_BOVIN DDAH1_BOVIN] Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
 +
== 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/ci/2ci5_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=2ci5 ConSurf].
 +
<div style="clear:both"></div>
 +
__TOC__
 +
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
-
[[Category: Dimethylargininase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Braun O]]
-
[[Category: Braun, O.]]
+
[[Category: Briand C]]
-
[[Category: Briand, C.]]
+
[[Category: Frey D]]
-
[[Category: Frey, D.]]
+
[[Category: Grutter MG]]
-
[[Category: Grutter, M G.]]
+
[[Category: Vasak M]]
-
[[Category: Vasak, M.]]
+
-
[[Category: CIT]]
+
-
[[Category: HCS]]
+
-
[[Category: acetylation]]
+
-
[[Category: adma]]
+
-
[[Category: hydrolase]]
+
-
[[Category: metal-binding]]
+
-
[[Category: mma]]
+
-
[[Category: no]]
+
-
[[Category: nos regulation]]
+
-
[[Category: s-nitrosylation]]
+
-
[[Category: zinc]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:48:52 2008''
+

Current revision

Crystal structure of Dimethylarginine Dimethylaminohydrolase I in complex with L-homocysteine

PDB ID 2ci5

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/2ci5"
Personal tools