View source for 7euk


==Crystal structure of N(omega)-hydroxy-L-arginine hydrolase in complex with L-Orn==
<StructureSection load='7euk' size='340' side='right'caption='[[7euk]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7euk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EUK 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]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=7euk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7euk OCA], [https://pdbe.org/7euk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7euk RCSB], [https://www.ebi.ac.uk/pdbsum/7euk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7euk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DCSB_STRLA DCSB_STRLA] Involved in the biosynthesis of the antibiotic D-cycloserine (DCS), a cyclic structural analog of D-alanine, used as an antitubercular agent. Catalyzes the hydrolysis of N(omega)-hydroxy-L-arginine (NHA) to yield hydroxyurea (HU) and L-ornithine.<ref>PMID:20086163</ref> <ref>PMID:22547619</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DcsB, an enzyme produced from the d-cycloserine biosynthetic gene cluster, displays moderate similarity to arginase in the sequence and three-dimensional structure. Arginase is a ubiquitous enzyme hydrolyzing l-arginine to generate l-ornithine and urea, whereas DcsB hydrolyzes N(omega) -hydroxy-l-arginine (l-NOHA), an arginase inhibitor, to generate l-ornithine and hydroxyurea. We determined the crystal structure of DcsB associated with l-ornithine and that with the tetrahedral derivative of 2(S)-amino-6-boronohexanoic acid, whose boron atom forms a covalent bond with an oxygen atom bridging two manganese ions at the active center. The substrate-binding pocket of DcsB is narrower than that of arginase, suggesting that DcsB is unsuitable for the binding of l-NOHA in an inhibitory manner. The transition state-like structure demonstrated that Asp210 and Glu241 have a role to trap a positively charged ion near the dimanganese cluster. Kinetic analysis using the mutated DcsB showed that the enzyme employs different catalytic mechanisms under the neutral and alkaline pH conditions. Glu241 in DcsB is likely involved in the recognition of the hydroxyguanidino group of l-NOHA, whereas Asp210, in cooperation with Glu241, seems to contribute to the reactivity toward the protonated l-NOHA, which is a preferable species under the neutral pH conditions. After entering of the protonated l-NOHA to the substrate-binding pocket of DcsB, a hydronium ion may be trapped at the positive ion-binding site. Then, the ion serves as a specific acid catalyst to facilitate the collapse of the tetrahedral intermediate of l-NOHA.

Catalytic mechanism of DcsB: Arginase framework used for hydrolyzing its inhibitor.,Oda K, Sakaguchi T, Matoba Y Protein Sci. 2022 Jun;31(6):e4338. doi: 10.1002/pro.4338. PMID:35634777<ref>PMID:35634777</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7euk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces lavendulae]]
[[Category: Matoba Y]]
[[Category: Oda K]]