|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of YwfH, NADPH dependent reductase involved in Bacilysin biosynthesis== | | ==Crystal structure of YwfH, NADPH dependent reductase involved in Bacilysin biosynthesis== |
| - | <StructureSection load='3u4d' size='340' side='right' caption='[[3u4d]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3u4d' size='340' side='right'caption='[[3u4d]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u4d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U4D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u4d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U4D FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u49|3u49]], [[3u4c|3u4c]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BSU37680, ipa-86r, ywfH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 "Vibrio subtilis" Ehrenberg 1835])</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=3u4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u4d OCA], [https://pdbe.org/3u4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u4d RCSB], [https://www.ebi.ac.uk/pdbsum/3u4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u4d 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=3u4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u4d OCA], [http://pdbe.org/3u4d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u4d RCSB], [http://www.ebi.ac.uk/pdbsum/3u4d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u4d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/YWFH_BACSU YWFH_BACSU]] Along with the bacABCDE operon is involved in bacilysin biosynthesis. | + | [https://www.uniprot.org/uniprot/BACG_BACSU BACG_BACSU] Along with the bacABCDEF operon, BacG is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. Bacilysin is an irreversible inactivator of the glutaminase domain of glucosamine synthetase (PubMed:20052993). BacG catalyzes the stereoselective reduction of exocyclic-delta(3),delta(5)-dihydro-hydroxyphenylpyruvate (ex-H2HPP), adding a pro-S hydride equivalent to C4 position to yield tetrahydro-hydroxyphenylpyruvate (H4HPP) (PubMed:22765234, PubMed:23519407). Although the 3Z,7R-ex-H2HPP isomer is kinetically disfavored by BacB and produced in a smaller quantity than 3E,7R-ex-H2HPP, it is the preferred substrate for the conjugate reduction reaction of BacG (PubMed:22765234, PubMed:23519407).<ref>PMID:20052993</ref> <ref>PMID:22765234</ref> <ref>PMID:23519407</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vibrio subtilis ehrenberg 1835]] | + | [[Category: Bacillus subtilis]] |
| - | [[Category: Gopal, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Rajavel, M]] | + | [[Category: Gopal B]] |
| - | [[Category: Bacilysin biosynthesis]] | + | [[Category: Rajavel M]] |
| - | [[Category: Nadph binding motif]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Sdr superfamily]]
| + | |
| Structural highlights
Function
BACG_BACSU Along with the bacABCDEF operon, BacG is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. Bacilysin is an irreversible inactivator of the glutaminase domain of glucosamine synthetase (PubMed:20052993). BacG catalyzes the stereoselective reduction of exocyclic-delta(3),delta(5)-dihydro-hydroxyphenylpyruvate (ex-H2HPP), adding a pro-S hydride equivalent to C4 position to yield tetrahydro-hydroxyphenylpyruvate (H4HPP) (PubMed:22765234, PubMed:23519407). Although the 3Z,7R-ex-H2HPP isomer is kinetically disfavored by BacB and produced in a smaller quantity than 3E,7R-ex-H2HPP, it is the preferred substrate for the conjugate reduction reaction of BacG (PubMed:22765234, PubMed:23519407).[1] [2] [3]
Publication Abstract from PubMed
The synthesis of the dipeptide antibiotic bacilysin involves the sequential action of multiple enzymes in the bac operon. YwfH (also referred to as BacG) catalyzes the stereoselective reduction of dihydro-hydroxyphenylpyruvate (H2HPP) to tetrahydro-hydroxyphenylpyruvate (H4HPP) in this biosynthetic pathway. YwfH is an NADPH-dependent reductase that facilitates the conjugate addition of a hydride at the C4 olefin terminus of H2HPP. Here, the structure of YwfH is described at three conformational steps: the apo form, an apo-like conformation and the NADPH complex. YwfH is structurally similar to other characterized short-chain dehydrogenase/reductases despite having marginal sequence similarity. The structures of YwfH in different conformational states provide a rationale for the ping-pong reaction mechanism. The identification and role of the residues in the catalytic tetrad (Lys113-Tyr117-Ser155-Asn158) in proton transfer were examined by mutational analysis. Together, the structures and biochemical features revealed synchronized conformational changes that facilitate cofactor specificity and catalysis of H4HPP formation en route to tetrahydrotyrosine synthesis.
Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis.,Rajavel M, Perinbam K, Gopal B Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):324-32. doi:, 10.1107/S0907444912046690. Epub 2013 Feb 16. PMID:23519407[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mahlstedt SA, Walsh CT. Investigation of anticapsin biosynthesis reveals a four-enzyme pathway to tetrahydrotyrosine in Bacillus subtilis. Biochemistry. 2010 Feb 9;49(5):912-23. PMID:20052993 doi:10.1021/bi9021186
- ↑ Parker JB, Walsh CT. Stereochemical outcome at four stereogenic centers during conversion of prephenate to tetrahydrotyrosine by BacABGF in the bacilysin pathway. Biochemistry. 2012 Jul 17;51(28):5622-32. PMID:22765234 doi:10.1021/bi3006362
- ↑ Rajavel M, Perinbam K, Gopal B. Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis. Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):324-32. doi:, 10.1107/S0907444912046690. Epub 2013 Feb 16. PMID:23519407 doi:http://dx.doi.org/10.1107/S0907444912046690
- ↑ Rajavel M, Perinbam K, Gopal B. Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis. Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):324-32. doi:, 10.1107/S0907444912046690. Epub 2013 Feb 16. PMID:23519407 doi:http://dx.doi.org/10.1107/S0907444912046690
|
