4m6y: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 3: | Line 3: | ||
<StructureSection load='4m6y' size='340' side='right'caption='[[4m6y]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4m6y' size='340' side='right'caption='[[4m6y]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4m6y]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4m6y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_hygroscopicus Streptomyces hygroscopicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M6Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M6Y FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=56D:(3R)-2-OXO-3-PHENYLBUTANOIC+ACID'>56D</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HF2:(2R)-2-HYDROXY-3-PHENYLPROPANOIC+ACID'>HF2</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=56D:(3R)-2-OXO-3-PHENYLBUTANOIC+ACID'>56D</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HF2:(2R)-2-HYDROXY-3-PHENYLPROPANOIC+ACID'>HF2</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=4m6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m6y OCA], [https://pdbe.org/4m6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m6y RCSB], [https://www.ebi.ac.uk/pdbsum/4m6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m6y ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MPPJ_STRHY MPPJ_STRHY] S-adenosyl-L-methionine-dependent methyltransferase involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[SAM-dependent | *[[SAM-dependent methyltrasferase 3D structures|SAM-dependent methyltrasferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Streptomyces hygroscopicus]] | ||
[[Category: | [[Category: Chan HC]] | ||
[[Category: | [[Category: Huang CJ]] | ||
[[Category: | [[Category: Li TL]] | ||
[[Category: | [[Category: Liu YC]] | ||
[[Category: | [[Category: Zou XW]] | ||
Latest revision as of 17:41, 8 November 2023
Mutant structure of methyltransferase from Streptomyces hygroscopicus complexed with S-adenosyl-L-homocysteine and methylphenylpyruvic acidMutant structure of methyltransferase from Streptomyces hygroscopicus complexed with S-adenosyl-L-homocysteine and methylphenylpyruvic acid
Structural highlights
FunctionMPPJ_STRHY S-adenosyl-L-methionine-dependent methyltransferase involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin. Publication Abstract from PubMedIn biological systems, methylation is most commonly performed by methyltransferases (MTs) using the electrophilic methyl source S-adenosyl-L-methionine (SAM) via the SN2 mechanism. (2S,3S)-beta-Methylphenylalanine, a nonproteinogenic amino acid, is a building unit of the glycopeptide antibiotic mannopeptimycin. The gene product of mppJ from the mannopeptimycin-biosynthetic gene cluster is the MT that methylates the benzylic C atom of phenylpyruvate (Ppy) to give betaMePpy. Although the benzylic C atom of Ppy is acidic, how its nucleophilicity is further enhanced to become an acceptor for C-methylation has not conclusively been determined. Here, a structural approach is used to address the mechanism of MppJ and to engineer it for new functions. The purified MppJ displays a turquoise colour, implying the presence of a metal ion. The crystal structures reveal MppJ to be the first ferric ion SAM-dependent MT. An additional four structures of binary and ternary complexes illustrate the molecular mechanism for the metal ion-dependent methyltransfer reaction. Overall, MppJ has a nonhaem iron centre that bind, orients and activates the alpha-ketoacid substrate and has developed a sandwiched bi-water device to avoid the formation of the unwanted reactive oxo-iron(IV) species during the C-methylation reaction. This discovery further prompted the conversion of the MT into a structurally/functionally unrelated new enzyme. Through stepwise mutagenesis and manipulation of coordination chemistry, MppJ was engineered to perform both Lewis acid-assisted hydration and/or O-methyltransfer reactions to give stereospecific new compounds. This process was validated by six crystal structures. The results reported in this study will facilitate the development and design of new biocatalysts for difficult-to-synthesize biochemicals. Structure and mechanism of a nonhaem-iron SAM-dependent C-methyltransferase and its engineering to a hydratase and an O-methyltransferase.,Zou XW, Liu YC, Hsu NS, Huang CJ, Lyu SY, Chan HC, Chang CY, Yeh HW, Lin KH, Wu CJ, Tsai MD, Li TL Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1549-60. doi:, 10.1107/S1399004714005239. Epub 2014 May 23. PMID:24914966[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||