View source for 7cxv


==Crystal structure of CmnK==
<StructureSection load='7cxv' size='340' side='right'caption='[[7cxv]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7cxv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharothrix_mutabilis_subsp._capreolus Saccharothrix mutabilis subsp. capreolus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXV 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]] 2.35&#8491;</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=7cxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxv OCA], [https://pdbe.org/7cxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxv RCSB], [https://www.ebi.ac.uk/pdbsum/7cxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A6YEI2_STRMP A6YEI2_STRMP] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Capreomycin (CMN) and viomycin (VIO) are nonribosomal peptide antituberculosis antibiotics, the structures of which contain four nonproteinogenic amino acids, including l-2,3-diaminopropionic acid (l-Dap), beta-ureidodehydroalanine, l-capreomycidine, and beta-lysine. Previous bioinformatics analysis suggested that CmnB/VioB and CmnK/VioK participate in the formation of l-Dap; however, the real substrates of these enzymes are yet to be confirmed. We herein show that starting from O-phospho-l-Ser (OPS) and l-Glu precursors, CmnB catalyzes the condensation reaction to generate a metabolite intermediate N-(1-amino-1-carboxyl-2-ethyl)glutamic acid (ACEGA), which undergoes NAD(+)-dependent oxidative hydrolysis by CmnK to generate l-Dap. Furthermore, the binding site of ACEGA and the catalytic mechanism of CmnK were elucidated with the assistance of three crystal structures, including those of apo-CmnK, the NAD(+)-CmnK complex, and CmnK in an alternative conformation. The CmnK-ACEGA docking model revealed that the glutamate alpha-hydrogen points toward the nicotinamide moiety. It provides evidence that the reaction is dependent on hydride transfer to form an imine intermediate, which is subsequently hydrolyzed by a water molecule to produce l-Dap. These findings modify the original proposed pathway and provide insights into l-Dap formation in the biosynthesis of other related natural products.

Characterization of Enzymes Catalyzing the Formation of the Nonproteinogenic Amino Acid l-Dap in Capreomycin Biosynthesis.,Hsu SH, Zhang S, Huang SC, Wu TK, Xu Z, Chang CY Biochemistry. 2021 Jan 12;60(1):77-84. doi: 10.1021/acs.biochem.0c00808. Epub, 2020 Dec 23. PMID:33356147<ref>PMID:33356147</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7cxv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharothrix mutabilis subsp. capreolus]]
[[Category: Chang CY]]
[[Category: Hsu SH]]