1-Aminocyclopropane-1-carboxylate synthase

Class of enzymes 1-aminocyclopropane-1-carboxylate synthase 4.4.1.14 72506-68-4 0016847 ACS white background.png Structure of ACC Synthase The enzyme aminocyclopropane-1-carboxylic acid synthase (ACC synthase, ACS) (EC 4.4.1.14) catalyzes the synthesis of 1-Aminocyclopropane-1-carboxylic acid (ACC), a precursor for ethylene, from S-Adenosyl methionine (AdoMet, SAM), an intermediate in the Yang cycle and activated methyl cycle and a useful molecule for methyl transfer: S-adenosyl-L-methionine = 1-aminocyclopropane-1-carboxylate + S-methyl-5-thioadenosine Like other PLP dependent enzymes, it catalyzes the reaction through a quinonoid zwitterion intermediate and uses cofactor pyridoxal phosphate (PLP, the active form of vitamin B6) for stabilization.Zhang Z, Ren JS, Clifton IJ, Schofield CJ Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase—the ethylene-forming enzyme Chem. Biol. 11 10 1383–94 October 2004 15489165 10.1016/j.chembiol.2004.08.012 free Capitani G, Hohenester E, Feng L, Storici P, Kirsch JF, Jansonius JN Structure of 1-aminocyclopropane-1-carboxylate synthase, a key enzyme in the biosynthesis of the plant hormone ethylene J. Mol. Biol. 294 3 745–56 December 1999 10610793 10.1006/jmbi.1999.3255 Huai Q, Xia Y, Chen Y, Callahan B, Li N, Ke H Crystal structures of 1-aminocyclopropane-1-carboxylate (ACC) synthase in complex with aminoethoxyvinylglycine and pyridoxal-5'-phosphate provide new insight into catalytic mechanisms J. Biol. Chem. 276 41 38210–6 11431475 10.1074/jbc.M103840200 October 2001 free This enzyme belongs to the family of lyases, specifically carbon-sulfur lyases. The systematic name of this enzyme class is S-adenosyl-L-methionine S-methyl-5-thioadenosine-lyase (1-aminocyclopropane-1-carboxylate-forming). Other names in common use include 1-aminocyclopropanecarboxylate synthase, 1-aminocyclopropane-1-carboxylic acid synthase, 1-aminocyclopropane-1-carboxylate synthetase, aminocyclopropanecarboxylic acid synthase, aminocyclopropanecarboxylate synthase, ACC synthase, and ''S''-adenosyl-L-methionine methylthioadenosine-lyase. This enzyme participates in propanoate metabolism. It employs one cofactor, pyridoxal phosphate. Enzyme mechanism thumb|300px|ACC Synthase Complex with PLP thumb|300px|ACC Synthase Complex with PLP: Catalytic Domain left|thumb|200px|Formation of the ACS-PLP Schiff Base. left|thumb|200px|Lys to SAM Imine Exchange. left|thumb|200px|Formation of the Quinonoid Intermediate. left|thumb|200px|Tyrosine and PLP stabilized 3C-Ring formation. The reaction catalyzed by 1-aminocyclopropane-1-carboxylic acid synthase (ACS) is the committed and rate-limiting step in the biosynthesis of ethylene [20], a gaseous plant hormone that is responsible for the initiation of fruit ripening, shoot and root growth and differentiation, leaf and fruit abscission, flower opening, and flower and leaf senescence. (source) It is a pyridoxal phosphate (PLP) dependent gamma-elimination (?). In the gamma elimination, PLP acts as a sink twice (absorbing electrons from two deprotonations).Li JF, Qu LH, Li N Tyr152 plays a central role in the catalysis of 1-aminocyclopropane-1-carboxylate synthase J. Exp. Bot. 56 418 2203–10 August 2005 15983009 10.1093/jxb/eri220 free Capitani G, McCarthy DL, Gut H, Grütter MG, Kirsch JF Apple 1-aminocyclopropane-1-carboxylate synthase in complex with the inhibitor L-aminoethoxyvinylglycine. Evidence for a ketimine intermediate J. Biol. Chem. 277 51 49735–42 12228256 10.1074/jbc.M208427200 December 2002 1019316 free Proposed steps of the reaction mechanism: Formation of the ACS-PLP Schiff Base Imine Exchange Formation of the Quinonoid Intermediate Tyrosine and PLP stabilized 3C-Ring formation Formation of the ACS-PLP Schiff Base The aldehyde of coenzyme PLP reacts to form an imine (Schiff base) linkage with the catalytic domain lysine (278) residue of ACS. Imine exchange An imine exchange occurs, and the amine nitrogen of the substrate, S-Adenosyl methionine, replaces Lys (278) in the imine linkage. (Stabilized by H bonding). Formation of the Quinonoid Intermediate PLP acts as an 'electron sink' absorbing delocalized electron density during the reaction intermediates (countering the excess electron density on the deprotonated a-carbon). PLP facilitates the enzyme activity, increasing the acidity of the alpha carbon by stabilizing the conjugate base. The PLP-stabilized carbanion intermediate formed is the quinonoid intermediate. Tyrosine and PLP stabilized 3C-Ring formation PLP and Tyrosine stabilize negative charges during deprotonation. Tyrosine attacks the sulfur bound carbon, allowing S(CH3)(Ado) to leave, and during ring formation, Tyrosine leaves. Note inhibitors AVG and AMA bind PLP to form a ketimine and oxime respectively (whose reverse reactions are much less favorable) and prevent the ACC synthase catalyzed reaction with SAM.Wang KL, Li H, Ecker JR Ethylene biosynthesis and signaling networks Plant Cell 14 Suppl S131–51 2002 Suppl 12045274 151252 10.1105/tpc.001768 2002PlanC..14S.131W Regulation ACC synthase reaches optimal activity in conditions of pH 8.5 and with Km = 20 um relative to its substrate, SAM. ACC Synthase and ethylene biosynthesis are regulated by a whole host of stimuli. Stresses such as wounding, noxious chemicals, auxin, flooding, and indole-3-acetic acid (IAA) promote ethylene synthesis, creating a positive feedback cycle with ACC synthase, up-regulating its activity. However, it is also inhibited by a number of compounds as well. S-Adenosylethionine can bind as a substrate for ACC synthase (with higher affinity than SAM) and therefore inhibit any reaction with SAM. ACC Synthase is also competitively inhibited by aminoethoxyvinylglycine (AVG) and aminooxyacetic acid (AOA), inhibitors to many pyridoxal phosphate-mediated enzymic reactions. They are natural toxins that cause slow binding inhibition by interfering with the coenzyme pyridoxal phosphate. ACC synthase activity is also inhibited by intermediates of the activated methyl cycle and the methionine-recycling pathway: 5-methylthioadenosine, α-keto-γ-methylthiobutyric acid, and S-adenosylhomocysteine.Yip WK, Moore T, Yang SF Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions Proc. Natl. Acad. Sci. U.S.A. 89 6 2475–9 March 1992 1549612 48681 10.1073/pnas.89.6.2475 1992PNAS...89.2475Y free Acaster MA, Kende H Properties and Partial Purification of 1-Aminocyclopropane-1-carboxylate Synthase Plant Physiol. 72 1 139–45 May 1983 16662947 1066183 10.1104/pp.72.1.139Lewis DR, Negi S, Sukumar P, Muday GK Ethylene inhibits lateral root development, increases IAA transport and expression of PIN3 and PIN7 auxin efflux carriers Development 138 16 3485–95 21771812 10.1242/dev.065102 August 2011 7211767 free Structure ACC Synthase is 450-516 amino acid long sequence depending on the species of plant from which it is extracted. Though it is comparable in the species in which it is found, its COOH-terminal domain is more variable, leading to differences such as oligomerization. The COOH-terminal domain is responsible for oligomerization. In most ACC Synthase producing cells, ACC Synthase exists as a dimer. However, in some we find a monomer ("which is more active and efficient [than its dimer counterpart").Kathiresan A, Nagarathna KC, Moloney MM, Reid DM, Chinnappa CC Differential regulation of 1-aminocyclopropane-1-carboxylate synthase gene family and its role in phenotypic plasticity in Stellaria longipes Plant Mol. Biol. 36 2 265–74 9484438 10.1023/A:1005994118535 January 1998 9161137 The structure of ACS has been largely determined via X-ray crystallography. Conservation of the residues in ACS's catalytic domain and sequence homology suggest that ACS catalyzes the synthesis of ACC in a similar fashion as other enzymes that require PLP as a cofactor. However, unlike many other PLP-dependent enzymes, Lys (278) is not the only residue that interacts with the substrate. The proximity of the electronegative oxygen from Tyr (152) to the C-γ-S bond suggests a crucial role in the formation of ACC. X-ray crystallography with aminoethoxyvinylglycine (AVG) a competitive inhibitor confirmed Tyrosine's role in the γ elimination.Yip WK, Moore T, Yang SF Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions Proc. Natl. Acad. Sci. U.S.A. 89 6 2475–9 1549612 48681 10.1073/pnas.89.6.2475 March 1992 1992PNAS...89.2475Y free As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes 1B8G, 1IAX, 1IAY, 1M4N, 1M7Y, and 1YNU. thumb|Lysine and Tyrosine Residues in the Substrate Binding Site Catalytic domain The main functional groups in the catalytic domains are the Nitrogen from the Lys 278 residue and the Oxygen from the Tyrosine 152 residue. Biological function and applications ACC Synthase is the key, rate limiting step in ethylene synthesis. Because the up-regulation of ACC-Synthase is what induces fruit ripening and often spoilage there is more research being done on the regulatory mechanisms and biosynthetic pathways of ethylene to avoid spoilage.Nakatsuka A, Murachi S, Okunishi H Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening Plant Physiol. 118 4 1295–305 9847103 34745 10.1104/pp.118.4.1295 December 1998 etal Notes 2 References Glycerol Kinase, the Pacemaker for the Dissimilation of Glycerol in Escherichia coli Journal of Bacteriology 102 3 753–759 June 1970 Lin E. C. C. Kistler W. S. Zwaig N. 10.1128/JB.102.3.753-759.1970 4914079 247623 free Differential Expression and Internal Feedback Regulation of 1-Aminocyclopropane-1-Carboxylate Synthase, 1-Aminocyclopropane-1-Carboxylate Oxidase, and Ethylene Receptor Genes in Tomato Fruit during Development and Ripening Plant Physiology 118 4 1295–1305 10.1104/pp.118.4.1295 1998 Nakatsuka Akira Murachi Shiho Okunishi Hironori Shiomi Shinjiro Nakano Ryohei Kubo Yasutaka Inaba Akitsugu 34745 9847103 1-Aminocyclopropane-1-carboxylic acid synthase 2 is phosphorylated by calcium-dependent protein kinase 1 during cotton fiber elongation Acta Biochimica et Biophysica Sinica 43 8 654–661 10.1093/abbs/gmr056 21742672 2011 Wang H. Mei W. Qin Y. Zhu Y. free Identification of Novel Inhibitors of 1-Aminocyclopropane-1-carboxylic Acid Synthase by Chemical Screening in Arabidopsis thaliana 10.1074/jbc.M110.132498 20682786 285 43 Journal of Biological Chemistry 33445–33456 2963424 2010-10-22 Wang Long-Chi Hsu Jen-Hung Lin Lee-Chung free Wang Kevin L.-C. Li Hai Ecker Joseph R. 2002-05-01 Ethylene Biosynthesis and Signaling Networks https://doi.org/10.1105/tpc.001768 The Plant Cell 14 suppl_1 S131–S151 10.1105/tpc.001768 1040-4651 151252 12045274 http://www.bioc.uzh.ch/gruetter/publications_files/2005/capitani_b.pdf Structure of ACC synthase inactivated by the mechanism-based inhibitor L-vinylglycine www.bioc.uzh.ch Guido Capitani Markus Tschopp Andrew C. Eliot Jack F. Kirsch Markus G. Grütter 2012-03-15 http://jxb.oxfordjournals.org/content/56/418/2203.full.pdf jxb.oxfordjournals.orgOctober 2026 jxb.oxfordjournals.org Journal of Experimental Botany 56 418 2203–2210 10.1093/jxb/eri220 15983009 2005 Li Jian-Feng Qu Liang-Hu Li Ning free Koga Y, Katsumi R, You DJ, Matsumura H, Takano K, Kanaya S Crystal structure of highly thermostable glycerol kinase from a hyperthermophilic archaeon in a dimeric form FEBS J. 275 10 2632–43 18422647 10.1111/j.1742-4658.2008.06410.x May 2008 205878773 free Nakatsuka A, Murachi S, Okunishi H Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening Plant Physiol. 118 4 1295–305 9847103 34745 10.1104/pp.118.4.1295 December 1998 etal Wang H, Mei W, Qin Y, Zhu Y 1-Aminocyclopropane-1-carboxylic acid synthase 2 is phosphorylated by calcium-dependent protein kinase 1 during cotton fiber elongation Acta Biochim. Biophys. Sin. (Shanghai) 43 8 654–61 21742672 10.1093/abbs/gmr056 August 2011 free Capitani G, Tschopp M, Eliot AC, Kirsch JF, Grütter MG Structure of ACC synthase inactivated by the mechanism-based inhibitor L-vinylglycine FEBS Lett. 579 11 2458–62 15848188 10.1016/j.febslet.2005.03.048 April 2005 24574380 free 2005FEBSL.579.2458C Li JF, Qu LH, Li N Tyr152 plays a central role in the catalysis of 1-aminocyclopropane-1-carboxylate synthase J. Exp. Bot. 56 418 2203–10 15983009 10.1093/jxb/eri220 August 2005 free Capitani G, McCarthy DL, Gut H, Grütter MG, Kirsch JF Apple 1-aminocyclopropane-1-carboxylate synthase in complex with the inhibitor L-aminoethoxyvinylglycine. Evidence for a ketimine intermediate J. Biol. Chem. 277 51 49735–42 12228256 10.1074/jbc.M208427200 December 2002 1019316 free Huai Q, Xia Y, Chen Y, Callahan B, Li N, Ke H Crystal structures of 1-aminocyclopropane-1-carboxylate (ACC) synthase in complex with aminoethoxyvinylglycine and pyridoxal-5'-phosphate provide new insight into catalytic mechanisms J. Biol. Chem. 276 41 38210–6 11431475 10.1074/jbc.M103840200 October 2001 free Barry CS, Llop-Tous MI, Grierson D The regulation of 1-aminocyclopropane-1-carboxylic acid synthase gene expression during the transition from system-1 to system-2 ethylene synthesis in tomato Plant Physiol. 123 3 979–86 10889246 59060 10.1104/pp.123.3.979 July 2000 Zhang Z, Ren JS, Clifton IJ, Schofield CJ Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase--the ethylene-forming enzyme Chem. Biol. 11 10 1383–94 15489165 10.1016/j.chembiol.2004.08.012 October 2004 free Capitani G, Hohenester E, Feng L, Storici P, Kirsch JF, Jansonius JN Structure of 1-aminocyclopropane-1-carboxylate synthase, a key enzyme in the biosynthesis of the plant hormone ethylene J. Mol. Biol. 294 3 745–56 10610793 10.1006/jmbi.1999.3255 December 1999 Holland RR Decision tables. Their use for the presentation of clinical algorithms JAMA 233 5 455–7 1080212 10.1001/jama.1975.03260050061028 August 1975 Kathiresan A, Nagarathna KC, Moloney MM, Reid DM, Chinnappa CC Differential regulation of 1-aminocyclopropane-1-carboxylate synthase gene family and its role in phenotypic plasticity in Stellaria longipes Plant Mol. Biol. 36 2 265–74 9484438 10.1023/A:1005994118535 January 1998 9161137 Yip WK, Moore T, Yang SF Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions Proc. Natl. Acad. Sci. U.S.A. 89 6 2475–9 1549612 48681 10.1073/pnas.89.6.2475 March 1992 1992PNAS...89.2475Y free Acaster MA, Kende H Properties and Partial Purification of 1-Aminocyclopropane-1-carboxylate Synthase Plant Physiol. 72 1 139–45 16662947 1066183 10.1104/pp.72.1.139 May 1983 Lewis DR, Negi S, Sukumar P, Muday GK Ethylene inhibits lateral root development, increases IAA transport and expression of PIN3 and PIN7 auxin efflux carriers Development 138 16 3485–95 21771812 10.1242/dev.065102 August 2011 7211767 free Clausen T, Huber R, Messerschmidt A, Pohlenz HD, Laber B Slow-binding inhibition of Escherichia coli cystathionine beta-lyase by L-aminoethoxyvinylglycine: a kinetic and X-ray study Biochemistry 36 41 12633–43 9376370 10.1021/bi970630m October 1997 Wang KL, Li H, Ecker JR Ethylene biosynthesis and signaling networks Plant Cell 14 Suppl S131–51 2002 Suppl 12045274 151252 10.1105/tpc.001768 2002PlanC..14S.131W Boller T, Herner RC, Kende H 1979 Assay for and enzymatic formation of an ethylene precursor, 1-aminocyclopropane-1-carboxylic acid Planta 145 293–303 10.1007/BF00454455 24317737 3 1979Plant.145..293B 27464828 Yu YB, Adams DO, Yang SF 1979 1-Aminocyclopropanecarboxylate synthase, a key enzyme in ethylene biosynthesis Arch. Biochem. Biophys. 198 280–6 507845 10.1016/0003-9861(79)90420-X 1 free Biology no Category:EC 4.4.1 Category:Pyridoxal phosphate enzymes Category:Enzymes of known structure