Citrate synthase family

Citrate_synt
PDB 1a59 EBI.jpg
cold-active citrate synthase
Identifiers
Symbol Citrate_synt
Pfam PF00285
InterPro IPR002020
PROSITE PDOC00422
SCOP 1csc

In molecular biology, the citrate synthase family of proteins includes the enzymes citrate synthase EC 2.3.3.1, and the related enzymes 2-methylcitrate synthase EC 2.3.3.5 and ATP citrate synthase EC 2.3.3.8.

Citrate synthase is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).

Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large alpha-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small alpha-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site.[1] The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal beta-sheet domain, and some type II enzymes are allosterically inhibited by NADH.[2]

2-methylcitrate synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive.[3]

ATP citrate synthase (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide.[4] ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate.[5]


References

  1. ^ Daidone I, Roccatano D, Hayward S (June 2004). "Investigating the accessibility of the closed domain conformation of citrate synthase using essential dynamics sampling". J. Mol. Biol. 339 (3): 515–25. doi:10.1016/j.jmb.2004.04.007. PMID 15147839. 
  2. ^ Francois JA, Starks CM, Sivanuntakorn S, Jiang H, Ransome AE, Nam JW, Constantine CZ, Kappock TJ (November 2006). "Structure of a NADH-insensitive hexameric citrate synthase that resists acid inactivation". Biochemistry 45 (45): 13487–99. doi:10.1021/bi061083k. PMID 17087502. 
  3. ^ Gerike U, Hough DW, Russell NJ, Dyall-Smith ML, Danson MJ (April 1998). "Citrate synthase and 2-methylcitrate synthase: structural, functional and evolutionary relationships". Microbiology (Reading, Engl.) 144 ( Pt 4): 929–35. PMID 9579066. 
  4. ^ Kim W, Tabita FR (September 2006). "Both subunits of ATP-citrate lyase from Chlorobium tepidum contribute to catalytic activity". J. Bacteriol. 188 (18): 6544–52. doi:10.1128/JB.00523-06. PMC 1595482. PMID 16952946. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1595482. 
  5. ^ Bauer DE, Hatzivassiliou G, Zhao F, Andreadis C, Thompson CB (September 2005). "ATP citrate lyase is an important component of cell growth and transformation". Oncogene 24 (41): 6314–22. doi:10.1038/sj.onc.1208773. PMID 16007201. 

This article includes text from the public domain Pfam and InterPro IPR002020


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • ATP citrate synthase — In enzymology, an ATP citrate synthase (EC number|2.3.3.8) is an enzyme that catalyzes the chemical reaction:ADP + phosphate + acetyl CoA + oxaloacetate ightleftharpoons ATP + citrate + CoAThe 4 substrates of this enzyme are ADP, phosphate,… …   Wikipedia

  • Citrate (Re)-synthase — Identifiers EC number 2.3.3.3 CAS number 9077 70 7 …   Wikipedia

  • p300-CBP coactivator family — E1A binding protein p300 Crystallographic structure of the histone acetyltrans ferase domain of EP300 (rainbow colored, N terminus = blue, C terminus = red) complexed with the inhibitor lysine CoA (space filling model, carbon = white, oxygen =… …   Wikipedia

  • ATP synthase — Molecular model of ATP synthase by X ray diffraction method ATP synthase (EC 3.6.3.14) is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate (ATP). ATP is the most commonly used energy… …   Wikipedia

  • Holo-ACP synthase — In enzymology, a holo ACP synthase (EC number|2.7.7.61) is an enzyme that catalyzes the chemical reaction:2 (5 triphosphoribosyl) 3 dephospho CoA + apo citrate lyase ightleftharpoons holo citrate lyase + diphosphateThus, the two substrates of… …   Wikipedia

  • Cystathionine beta synthase — Structure of human cystathionine beta synthase.[1] …   Wikipedia

  • Aerobactin synthase — In enzymology, an aerobactin synthase (EC number|6.3.2.27) is an enzyme that catalyzes the chemical reaction:4 ATP + citrate + 2 N6 acetyl N6 hydroxy L lysine + 2 H2O ightleftharpoons 4 ADP + 4 phosphate + aerobactinThe 4 substrates of this… …   Wikipedia

  • N-Acetylglutamate synthase deficiency — Classification and external resources N Acetylglutamic acid OMIM 237310 …   Wikipedia

  • 2-oxoglutarate synthase — In enzymology, a 2 oxoglutarate synthase (EC number|1.2.7.3) is an enzyme that catalyzes the chemical reaction:2 oxoglutarate + CoA + 2 oxidized ferredoxin ightleftharpoons succinyl CoA + CO2 + 2 reduced ferredoxinThe 3 substrates of this enzyme… …   Wikipedia

  • metabolism — /meuh tab euh liz euhm/, n. 1. Biol., Physiol. the sum of the physical and chemical processes in an organism by which its material substance is produced, maintained, and destroyed, and by which energy is made available. Cf. anabolism, catabolism …   Universalium

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.