8ovh

From Proteopedia

(Difference between revisions)

Revision as of 09:42, 21 June 2023

Crystal structure of O-acetyl-L-homoserine sulfhydrolase from Saccharomyces cerevisiae in complex with Pyridoxal-5'-phosphate

Structural highlights

8ovh is a 4 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CYSD_YEAST Catalyzes the conversion of O-acetyl-L-homoserine (OAH) into homocysteine in the methionine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053, PubMed:36379252). Required to efficiently reduce toxic levels of hydrogen sulfide generated when the sulfate assimilation pathway (SAP) is active (PubMed:36455053, PubMed:36379252). Also catalyzes the conversion of O-acetylserine (OAS) into cysteine, the last step in the cysteine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053). However, it seems that in S.cerevisiae cysteine biosynthesis occurs exclusively through the cystathionine pathway and not via direct incorporation of sulfur into OAS (PubMed:1732168). It therefore has no metabolic role in cysteine biosynthesis and may only have a regulatory role controlling OAS levels (PubMed:12586406).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Chemical modification of small molecules is a key step for the development of pharmaceuticals. S-adenosyl-l-methionine (SAM) analogues are used by methyltransferases (MTs) to transfer alkyl, allyl and benzyl moieties chemo-, stereo- and regioselectively onto substrates, enabling an enzymatic way for specific derivatisation of a wide range of molecules. l-Methionine analogues are required for the synthesis of SAM analogues. Most of these are not commercially available. In nature, O-acetyl-l-homoserine sulfhydrolases (OAHS) catalyse the synthesis of l-methionine from O-acetyl-l-homoserine or l-homocysteine, and methyl mercaptan. Here, we investigated the substrate scope of ScOAHS from Saccharomyces cerevisiae for the production of l-methionine analogues from l-homocysteine and organic thiols. The promiscuous enzyme was used to synthesise nine different l-methionine analogues with modifications on the thioether residue up to a conversion of 75%. ScOAHS was combined with an established MT dependent three-enzyme alkylation cascade, allowing transfer of in total seven moieties onto two MT substrates. Ethylation was nearly doubled with the new four-enzyme cascade, indicating a beneficial effect of the in situ production of l-methionine analogues with ScOAHS.

Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade.,Mohr MKF, Saleem-Batcha R, Cornelissen NV, Andexer JN Chemistry. 2023 May 26:e202301503. doi: 10.1002/chem.202301503. PMID:37235813^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Van Oss SB, Parikh SB, Castilho Coelho N, Wacholder A, Belashov I, Zdancewicz S, Michaca M, Xu J, Kang YP, Ward NP, Yoon SJ, McCourt KM, McKee J, Ideker T, VanDemark AP, DeNicola GM, Carvunis AR. On the illusion of auxotrophy: met15Δ yeast cells can grow on inorganic sulfur, thanks to the previously uncharacterized homocysteine synthase Yll058w. J Biol Chem. 2022 Dec;298(12):102697. PMID:36379252 doi:10.1016/j.jbc.2022.102697
↑ Yu JSL, Heineike BM, Hartl J, Aulakh SK, Correia-Melo C, Lehmann A, Lemke O, Agostini F, Lee CT, Demichev V, Messner CB, Mülleder M, Ralser M. Inorganic sulfur fixation via a new homocysteine synthase allows yeast cells to cooperatively compensate for methionine auxotrophy. PLoS Biol. 2022 Dec 1;20(12):e3001912. PMID:36455053 doi:10.1371/journal.pbio.3001912
↑ Yamagata S, Takeshima K, Naiki N. Evidence for the identity of O-acetylserine sulfhydrylase with O-acetylhomoserine sulfhydrylase in yeast. J Biochem. 1974 Jun;75(6):1221-9. PMID:4609980 doi:10.1093/oxfordjournals.jbchem.a130505
↑ Yamagata S, Isaji M, Nakamura K, Fujisaki S, Doi K, Bawden S, D'Andrea R. Overexpression of the Saccharomyces cerevisiae MET17/MET25 gene in Escherichia coli and comparative characterization of the product with O-acetylserine.O-acetylhomoserine sulfhydrylase of the yeast. Appl Microbiol Biotechnol. 1994 Oct;42(1):92-9. PMID:7765825 doi:10.1007/BF00170230
↑ Yamagata S, Takeshima K. O-Acetylserine and O-acetylhomoserine sulfhydrylase of yeast. Further purification and characterization as a pyridoxal enzyme. J Biochem. 1976 Oct;80(4):777-85. PMID:795806 doi:10.1093/oxfordjournals.jbchem.a131338
↑ Takagi H, Yoshioka K, Awano N, Nakamori S, Ono Bi. Role of Saccharomyces cerevisiae serine O-acetyltransferase in cysteine biosynthesis. FEMS Microbiol Lett. 2003 Jan 28;218(2):291-7. PMID:12586406 doi:10.1111/j.1574-6968.2003.tb11531.x
↑ Cherest H, Surdin-Kerjan Y. Genetic analysis of a new mutation conferring cysteine auxotrophy in Saccharomyces cerevisiae: updating of the sulfur metabolism pathway. Genetics. 1992 Jan;130(1):51-8. PMID:1732168 doi:10.1093/genetics/130.1.51
↑ Mohr MKF, Saleem-Batcha R, Cornelissen NV, Andexer JN. Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade. Chemistry. 2023 May 26:e202301503. PMID:37235813 doi:10.1002/chem.202301503

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8ovh"

Categories: Large Structures | Saccharomyces cerevisiae | Andexer JN | Mohr M | Saleem-Batcha R

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ovh is ON HOLD
+==Crystal structure of O-acetyl-L-homoserine sulfhydrolase from Saccharomyces cerevisiae in complex with Pyridoxal-5'-phosphate==
+<StructureSection load='8ovh' size='340' side='right'caption='[[8ovh]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ovh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OVH FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=8ovh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ovh OCA], [https://pdbe.org/8ovh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ovh RCSB], [https://www.ebi.ac.uk/pdbsum/8ovh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ovh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CYSD_YEAST CYSD_YEAST] Catalyzes the conversion of O-acetyl-L-homoserine (OAH) into homocysteine in the methionine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053, PubMed:36379252). Required to efficiently reduce toxic levels of hydrogen sulfide generated when the sulfate assimilation pathway (SAP) is active (PubMed:36455053, PubMed:36379252). Also catalyzes the conversion of O-acetylserine (OAS) into cysteine, the last step in the cysteine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053). However, it seems that in S.cerevisiae cysteine biosynthesis occurs exclusively through the cystathionine pathway and not via direct incorporation of sulfur into OAS (PubMed:1732168). It therefore has no metabolic role in cysteine biosynthesis and may only have a regulatory role controlling OAS levels (PubMed:12586406).<ref>PMID:36379252</ref> <ref>PMID:36455053</ref> <ref>PMID:4609980</ref> <ref>PMID:7765825</ref> <ref>PMID:795806</ref> <ref>PMID:12586406</ref> <ref>PMID:1732168</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Chemical modification of small molecules is a key step for the development of pharmaceuticals. S-adenosyl-l-methionine (SAM) analogues are used by methyltransferases (MTs) to transfer alkyl, allyl and benzyl moieties chemo-, stereo- and regioselectively onto substrates, enabling an enzymatic way for specific derivatisation of a wide range of molecules. l-Methionine analogues are required for the synthesis of SAM analogues. Most of these are not commercially available. In nature, O-acetyl-l-homoserine sulfhydrolases (OAHS) catalyse the synthesis of l-methionine from O-acetyl-l-homoserine or l-homocysteine, and methyl mercaptan. Here, we investigated the substrate scope of ScOAHS from Saccharomyces cerevisiae for the production of l-methionine analogues from l-homocysteine and organic thiols. The promiscuous enzyme was used to synthesise nine different l-methionine analogues with modifications on the thioether residue up to a conversion of 75%. ScOAHS was combined with an established MT dependent three-enzyme alkylation cascade, allowing transfer of in total seven moieties onto two MT substrates. Ethylation was nearly doubled with the new four-enzyme cascade, indicating a beneficial effect of the in situ production of l-methionine analogues with ScOAHS.
-Authors:
+Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade.,Mohr MKF, Saleem-Batcha R, Cornelissen NV, Andexer JN Chemistry. 2023 May 26:e202301503. doi: 10.1002/chem.202301503. PMID:37235813<ref>PMID:37235813</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8ovh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Andexer JN]]
+[[Category: Mohr M]]
+[[Category: Saleem-Batcha R]]

8ovh

From Proteopedia

Revision as of 09:42, 21 June 2023

Crystal structure of O-acetyl-L-homoserine sulfhydrolase from Saccharomyces cerevisiae in complex with Pyridoxal-5'-phosphate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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