2.50
Hdl Handle:
http://hdl.handle.net/10033/620927
Title:
Crystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus.
Authors:
Bock, Tobias; Kasten, Janin; Müller, Rolf ( 0000-0002-1042-5665 ) ; Blankenfeldt, Wulf ( 0000-0001-9886-9668 )
Abstract:
A critical step in bacterial isoprenoid production is the synthesis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) catalyzed by HMG-CoA synthase (HMGCS). In myxobacteria, this enzyme is also involved in a recently discovered alternative and acetyl-CoA-dependent isovaleryl CoA biosynthesis pathway. Here we present crystal structures of MvaS, the HMGCS from Myxococcus xanthus, in complex with CoA and acetylated active site Cys115, with the second substrate acetoacetyl CoA and with the product of the condensation reaction, 3-hydroxy-3-methylglutaryl CoA. With these structures, we show that MvaS uses the common HMGCS enzymatic mechanism and provide evidence that dimerization plays a role in the formation and stability of the active site. Overall, MvaS shows features typical of the eukaryotic HMGCS and exhibits differences from homologues from Gram-positive bacteria. This study provides insights into myxobacterial alternative isovaleryl CoA biosynthesis and thereby extends the toolbox for the biotechnological production of renewable fuel and chemicals.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Crystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus. 2016, 17 (13):1257-62 Chembiochem
Journal:
Chembiochem : a European journal of chemical biology
Issue Date:
1-Jul-2016
URI:
http://hdl.handle.net/10033/620927
DOI:
10.1002/cbic.201600070
PubMed ID:
27124816
Type:
Article
Language:
en
ISSN:
1439-7633
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS); publications of the department of microbial natural substances ([HIPS]MINS); Publications of the Dept. Structure and Functions of Proteins(SFPR)

Full metadata record

DC FieldValue Language
dc.contributor.authorBock, Tobiasen
dc.contributor.authorKasten, Janinen
dc.contributor.authorMüller, Rolfen
dc.contributor.authorBlankenfeldt, Wulfen
dc.date.accessioned2017-05-22T14:01:14Z-
dc.date.available2017-05-22T14:01:14Z-
dc.date.issued2016-07-01-
dc.identifier.citationCrystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus. 2016, 17 (13):1257-62 Chembiochemen
dc.identifier.issn1439-7633-
dc.identifier.pmid27124816-
dc.identifier.doi10.1002/cbic.201600070-
dc.identifier.urihttp://hdl.handle.net/10033/620927-
dc.description.abstractA critical step in bacterial isoprenoid production is the synthesis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) catalyzed by HMG-CoA synthase (HMGCS). In myxobacteria, this enzyme is also involved in a recently discovered alternative and acetyl-CoA-dependent isovaleryl CoA biosynthesis pathway. Here we present crystal structures of MvaS, the HMGCS from Myxococcus xanthus, in complex with CoA and acetylated active site Cys115, with the second substrate acetoacetyl CoA and with the product of the condensation reaction, 3-hydroxy-3-methylglutaryl CoA. With these structures, we show that MvaS uses the common HMGCS enzymatic mechanism and provide evidence that dimerization plays a role in the formation and stability of the active site. Overall, MvaS shows features typical of the eukaryotic HMGCS and exhibits differences from homologues from Gram-positive bacteria. This study provides insights into myxobacterial alternative isovaleryl CoA biosynthesis and thereby extends the toolbox for the biotechnological production of renewable fuel and chemicals.en
dc.language.isoenen
dc.titleCrystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalChembiochem : a European journal of chemical biologyen

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