Literature summary for 2.3.1.9 extracted from

Voegeli, B.; Engilberge, S.; Girard, E.; Riobe, F.; Maury, O.; Erb, T.J.; Shima, S.; Wagner, T.
Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site (2018), Proc. Natl. Acad. Sci. USA, 115, 3380-3385 .

Crystallization (Commentary)

Crystallization (Comment)	Organism
acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl -CoA synthase HMGCS form a complex. HMGCS catalyzes the second reaction in the mevalonate pathway. The 380-kDa crystal structure reveals that both enzymes are held together by a third protein (DUF35) with so-far-unknown function. The active-site clefts of thiolase and HMGCS form a fused CoA-binding site, which allows for efficient coupling of the endergonic thiolase reaction with the exergonic HMGCS reaction. The thiolase/HMGCS complex alone is able to convert acetyl-CoA to HMG-CoA. The tripartite complex is found in almost all archaeal genomes and in some bacterial ones	Methanothermococcus thermolithotrophicus
sitting drop method, 18-20°C. The crystal structure of the native complex revealed a unique, shared CoA-binding site formed by both the acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase subunits thiolases (thiolases). A small scaffold protein connects the two enzymes	Methanothermococcus thermolithotrophicus

Crystallization (Comment)

Organism

acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl -CoA synthase HMGCS form a complex. HMGCS catalyzes the second reaction in the mevalonate pathway. The 380-kDa crystal structure reveals that both enzymes are held together by a third protein (DUF35) with so-far-unknown function. The active-site clefts of thiolase and HMGCS form a fused CoA-binding site, which allows for efficient coupling of the endergonic thiolase reaction with the exergonic HMGCS reaction. The thiolase/HMGCS complex alone is able to convert acetyl-CoA to HMG-CoA. The tripartite complex is found in almost all archaeal genomes and in some bacterial ones

Methanothermococcus thermolithotrophicus

sitting drop method, 18-20°C. The crystal structure of the native complex revealed a unique, shared CoA-binding site formed by both the acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase subunits thiolases (thiolases). A small scaffold protein connects the two enzymes

Methanothermococcus thermolithotrophicus

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
41900	-	mass spectrometric sequencing	Methanothermococcus thermolithotrophicus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2 acetyl-CoA	Methanothermococcus thermolithotrophicus	the enzyme catalyzes a reaction in the mevalonate pathway	CoA + acetoacetyl-CoA	-	?
2 acetyl-CoA	Methanothermococcus thermolithotrophicus DSM 2095	the enzyme catalyzes a reaction in the mevalonate pathway	CoA + acetoacetyl-CoA	-	?

Organism

Organism	UniProt	Comment	Textmining
Methanothermococcus thermolithotrophicus	-	-	-
Methanothermococcus thermolithotrophicus	A0A384E138	-	-
Methanothermococcus thermolithotrophicus DSM 2095	-	-	-
Methanothermococcus thermolithotrophicus DSM 2095	A0A384E138	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Methanothermococcus thermolithotrophicus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
2 acetyl-CoA	-	Methanothermococcus thermolithotrophicus	CoA + acetoacetyl-CoA	-	?
2 acetyl-CoA	the enzyme catalyzes a reaction in the mevalonate pathway	Methanothermococcus thermolithotrophicus	CoA + acetoacetyl-CoA	-	?
2 acetyl-CoA	-	Methanothermococcus thermolithotrophicus DSM 2095	CoA + acetoacetyl-CoA	-	?
2 acetyl-CoA	the enzyme catalyzes a reaction in the mevalonate pathway	Methanothermococcus thermolithotrophicus DSM 2095	CoA + acetoacetyl-CoA	-	?

Synonyms

Synonyms	Comment	Organism
acetoacetyl-CoA thiolase	-	Methanothermococcus thermolithotrophicus

General Information

General Information	Comment	Organism
metabolism	the enzyme catalyzes a reaction in the mevalonate pathway. Mevalonate is a building block of archaeal lipids. Three enzymes are involved in its biosynthesis: acetoacetyl-CoA thiolase (thiolase), 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS), and HMG-CoA reductase. The thiolase reaction is highly endergonic. In the thiolase/HMGCS complex, the endergonic thiolase reaction is directly coupled to the exergonic 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase reaction. A third protein spatially connects both enzymes. The two enzymes share the same substrate-binding site. Genomic information indicates that the presence of a thiolase/HMGCS complex is common in most of archaea and many bacteria	Methanothermococcus thermolithotrophicus