The crotonase family comprises mechanistically diverse proteins that share a conserved trimeric quaternary structure (sometimes a hexamer consisting of a dimer of trimers), the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix.
Some enzymes in the superfamily have been shown to display
dehalogenase,
hydratase, and
isomerase activities, while others have been implicated in carbon-carbon bond formation and cleavage as well as the hydrolysis of thioesters.[1] However, these different enzymes share the need to stabilize an
enolate anion intermediate derived from an
acyl-CoA substrate. This is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole". The
CoAthioester derivatives bind in a characteristic hooked shape and a conserved tunnel binds the pantetheine group of CoA, which links the 3'-phosphate ADP binding site to the site of reaction.[2] Enzymes in the crotonase superfamily include:
3-2trans-enoyl-CoA isomerase (or dodecenoyl-CoA isomerise;
EC5.3.3.8), which shifts the 3-double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position.[4]
6-oxo camphor hydrolase, which catalyses the desymmetrization of bicyclic beta-diketones to optically active keto acids.[11]
The alpha subunit of
fatty acid oxidation complex, a multi-enzyme complex that catalyses the last three reactions in the fatty acid beta-oxidation cycle.[12]
AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase.[13]
^Gerlt JA, Benning MM, Holden HM, Haller T (2001). "The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters". Acc. Chem. Res. 34 (2): 145–57.
doi:
10.1021/ar000053l.
PMID11263873.
^Brzozowski AM, Leonard PM, Bennett JP, Whittingham JL, Grogan G (2007). "Structural characterization of a beta-diketone hydrolase from the cyanobacterium Anabaena sp. PCC 7120 in native and product-bound forms, a coenzyme A-independent member of the crotonase suprafamily". Biochemistry. 46 (1): 137–44.
doi:
10.1021/bi061900g.
PMID17198383.
^Stoffel W, Muller-Newen G (1991). "Mitochondrial 3-2trans-Enoyl-CoA isomerase. Purification, cloning, expression, and mitochondrial import of the key enzyme of unsaturated fatty acid beta-oxidation". Biol. Chem. Hoppe-Seyler. 372 (8): 613–624.
doi:
10.1515/bchm3.1991.372.2.613.
PMID1958319.
^Dunaway-Mariano D, Benning MM, Wesenberg G, Holden HM, Taylor KL, Yang G, Liu R-Q, Xiang H (1996). "Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation". Biochemistry. 35 (25): 8103–9.
doi:
10.1021/bi960768p.
PMID8679561.
^Baker EN, Johnston JM, Arcus VL (2005). "Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms". Acta Crystallogr. D. 61 (Pt 9): 1199–206.
doi:
10.1107/S0907444905017531.
hdl:2292/9814.
PMID16131752.
^Kleber HP, Elssner T, Engemann C, Baumgart K (2001). "Involvement of coenzyme A esters and two new enzymes, an enoyl-CoA hydratase and a CoA-transferase, in the hydration of crotonobetaine to L-carnitine by Escherichia coli". Biochemistry. 40 (37): 11140–8.
doi:
10.1021/bi0108812.
PMID11551212.
^Gerlt JA, Benning MM, Holden HM, Haller T (2000). "New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli". Biochemistry. 39 (16): 4630–9.
doi:
10.1021/bi9928896.
PMID10769118.
^Resibois-Gregoire A, Dourov N (1966). "Electron microscopic study of a case of cerebral glycogenosis". Acta Neuropathol. 6 (1): 70–9.
doi:
10.1007/BF00691083.
PMID5229654.
S2CID21331079.
The crotonase family comprises mechanistically diverse proteins that share a conserved trimeric quaternary structure (sometimes a hexamer consisting of a dimer of trimers), the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix.
Some enzymes in the superfamily have been shown to display
dehalogenase,
hydratase, and
isomerase activities, while others have been implicated in carbon-carbon bond formation and cleavage as well as the hydrolysis of thioesters.[1] However, these different enzymes share the need to stabilize an
enolate anion intermediate derived from an
acyl-CoA substrate. This is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole". The
CoAthioester derivatives bind in a characteristic hooked shape and a conserved tunnel binds the pantetheine group of CoA, which links the 3'-phosphate ADP binding site to the site of reaction.[2] Enzymes in the crotonase superfamily include:
3-2trans-enoyl-CoA isomerase (or dodecenoyl-CoA isomerise;
EC5.3.3.8), which shifts the 3-double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position.[4]
6-oxo camphor hydrolase, which catalyses the desymmetrization of bicyclic beta-diketones to optically active keto acids.[11]
The alpha subunit of
fatty acid oxidation complex, a multi-enzyme complex that catalyses the last three reactions in the fatty acid beta-oxidation cycle.[12]
AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase.[13]
^Gerlt JA, Benning MM, Holden HM, Haller T (2001). "The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters". Acc. Chem. Res. 34 (2): 145–57.
doi:
10.1021/ar000053l.
PMID11263873.
^Brzozowski AM, Leonard PM, Bennett JP, Whittingham JL, Grogan G (2007). "Structural characterization of a beta-diketone hydrolase from the cyanobacterium Anabaena sp. PCC 7120 in native and product-bound forms, a coenzyme A-independent member of the crotonase suprafamily". Biochemistry. 46 (1): 137–44.
doi:
10.1021/bi061900g.
PMID17198383.
^Stoffel W, Muller-Newen G (1991). "Mitochondrial 3-2trans-Enoyl-CoA isomerase. Purification, cloning, expression, and mitochondrial import of the key enzyme of unsaturated fatty acid beta-oxidation". Biol. Chem. Hoppe-Seyler. 372 (8): 613–624.
doi:
10.1515/bchm3.1991.372.2.613.
PMID1958319.
^Dunaway-Mariano D, Benning MM, Wesenberg G, Holden HM, Taylor KL, Yang G, Liu R-Q, Xiang H (1996). "Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation". Biochemistry. 35 (25): 8103–9.
doi:
10.1021/bi960768p.
PMID8679561.
^Baker EN, Johnston JM, Arcus VL (2005). "Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms". Acta Crystallogr. D. 61 (Pt 9): 1199–206.
doi:
10.1107/S0907444905017531.
hdl:2292/9814.
PMID16131752.
^Kleber HP, Elssner T, Engemann C, Baumgart K (2001). "Involvement of coenzyme A esters and two new enzymes, an enoyl-CoA hydratase and a CoA-transferase, in the hydration of crotonobetaine to L-carnitine by Escherichia coli". Biochemistry. 40 (37): 11140–8.
doi:
10.1021/bi0108812.
PMID11551212.
^Gerlt JA, Benning MM, Holden HM, Haller T (2000). "New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli". Biochemistry. 39 (16): 4630–9.
doi:
10.1021/bi9928896.
PMID10769118.
^Resibois-Gregoire A, Dourov N (1966). "Electron microscopic study of a case of cerebral glycogenosis". Acta Neuropathol. 6 (1): 70–9.
doi:
10.1007/BF00691083.
PMID5229654.
S2CID21331079.