5zdn
From Proteopedia
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<StructureSection load='5zdn' size='340' side='right' caption='[[5zdn]], [[Resolution|resolution]] 2.02Å' scene=''> | <StructureSection load='5zdn' size='340' side='right' caption='[[5zdn]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5zdn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZDN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zdn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_fradii"_(sic)_waksman_and_curtis_1916 "actinomyces fradii" (sic) waksman and curtis 1916]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZDN FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fomD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1906 "Actinomyces fradii" (sic) Waksman and Curtis 1916])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zdn OCA], [http://pdbe.org/5zdn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zdn RCSB], [http://www.ebi.ac.uk/pdbsum/5zdn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zdn ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zdn OCA], [http://pdbe.org/5zdn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zdn RCSB], [http://www.ebi.ac.uk/pdbsum/5zdn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zdn ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In fosfomycin biosynthesis, the hydrolysis of cytidylyl ( S)-2-hydroxypropylphosphonate [( S)-HPP-CMP] to afford ( S)-HPP is the only uncharacterized step. Because FomD is an uncharacterized protein with a DUF402 domain that is encoded in the fosfomycin biosynthetic gene cluster, FomD was hypothesized to be responsible for this reaction. In this study, FomD was found to hydrolyze ( S)-HPP-CMP to give ( S)-HPP and CMP efficiently in the presence of Mn(2+) or Co(2+). FomD also hydrolyzed cytidylyl 2-hydroxyethylphosphonate (HEP-CMP), which is a biosynthetic intermediate before C-methylation. The kcat/ KM value of FomD with ( S)-HPP-CMP was 10-fold greater than that with HEP-CMP, suggesting that FomD hydrolyzes ( S)-HPP-CMP rather than HEP-CMP in bacteria. The crystal structure of FomD showed that this protein adopts a barrel-like fold, which consists of a large twisted antiparallel beta-sheet. This is a key structural feature of the DUF402 domain-containing proteins. Two metal cations are located between the FomD barrel and the two alpha-helices at the C-terminus and serve to presumably activate the phosphonate group of substrates for hydrolysis. Docking simulations with ( S)-HPP-CMP suggested that the methyl group at the C2 position of the HPP moiety is recognized by a hydrophobic interaction with Trp68. Further mutational analysis suggested that a conserved Tyr107 among the DUF402 domain family of proteins activates a water molecule to promote nucleophilic attack on the phosphorus atom of the phosphonate moiety. These findings provide mechanistic insights into the FomD reaction and lead to a complete understanding of the fosfomycin biosynthetic pathway in Streptomyces. | ||
| + | |||
| + | Biochemical and Structural Analysis of FomD That Catalyzes the Hydrolysis of Cytidylyl ( S)-2-Hydroxypropylphosphonate in Fosfomycin Biosynthesis.,Sato S, Miyanaga A, Kim SY, Kuzuyama T, Kudo F, Eguchi T Biochemistry. 2018 Aug 14;57(32):4858-4866. doi: 10.1021/acs.biochem.8b00690., Epub 2018 Jul 25. PMID:30010320<ref>PMID:30010320</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5zdn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:53, 29 August 2018
The complex structure of FomD with CDP
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Categories: Eguchi, T | Kudo, F | Miyanaga, A | Sato, S | Hydrolase | Metalloprotein
