“1-aminocyclopropane-1-carboxylate synthase”的意思、由来-开放百科全书

In enzymology, a 1-aminocyclopropane-1-carboxylate synthase is an enzyme that catalyzes the chemical reaction

Hence, this enzyme has one substrate, S-adenosyl-L-methionine, and two products, 1-aminocyclopropane-1-carboxylate and methylthioadenosine.

This enzyme belongs to the family of lyases, specifically carbon-sulfur lyases. The systematic name of this enzyme class is S-adenosyl-L-methionine methylthioadenosine-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

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).^[4]^[5]

The aldehyde of coenzyme PLP reacts to form an imine (Schiff base) linkage with the catalytic domain lysine (278) residue of ACS.

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).

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.

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.

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.^[8]^[9]^[10]

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").^[11]

The structure of ACS has been largely determined via X-ray crystallography.^[12] 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.^[13] X-ray crystallography with aminoethoxyvinylglycine (AVG) a competitive inhibitor confirmed Tyrosine's role in the γ elimination.^[14]

As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1B8G}}, {{PDB link|1IAX}}, {{PDB link|1IAY}}, {{PDB link|1M4N}}, {{PDB link|1M7Y}}, and {{PDB link|1YNU}}.

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.^[15]^[16]

Notes

1. ^{{cite journal |vauthors=Zhang Z, Ren JS, Clifton IJ, Schofield CJ |title=Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase--the ethylene-forming enzyme |journal=Chem. Biol. |volume=11 |issue=10 |pages=1383–94 |date=October 2004|pmid=15489165 |doi=10.1016/j.chembiol.2004.08.012 |url=}}
2. ^{{cite journal |vauthors=Capitani G, Hohenester E, Feng L, Storici P, Kirsch JF, Jansonius JN |title=Structure of 1-aminocyclopropane-1-carboxylate synthase, a key enzyme in the biosynthesis of the plant hormone ethylene |journal=J. Mol. Biol. |volume=294 |issue=3 |pages=745–56 |date=December 1999|pmid=10610793 |doi=10.1006/jmbi.1999.3255 |url=}}
3. ^{{cite journal |vauthors=Huai Q, Xia Y, Chen Y, Callahan B, Li N, Ke H |title=Crystal structures of 1-aminocyclopropane-1-carboxylate (ACC) synthase in complex with aminoethoxyvinylglycine and pyridoxal-5'-phosphate provide new insight into catalytic mechanisms |journal=J. Biol. Chem. |volume=276 |issue=41 |pages=38210–6 |pmid=11431475 |doi=10.1074/jbc.M103840200 |url=|date=October 2001}}
4. ^{{cite journal |vauthors=Li JF, Qu LH, Li N |title=Tyr152 plays a central role in the catalysis of 1-aminocyclopropane-1-carboxylate synthase |journal=J. Exp. Bot. |volume=56 |issue=418 |pages=2203–10 |date=August 2005|pmid=15983009 |doi=10.1093/jxb/eri220 |url=}}
5. ^{{cite journal |vauthors=Capitani G, McCarthy DL, Gut H, Grütter MG, Kirsch JF |title=Apple 1-aminocyclopropane-1-carboxylate synthase in complex with the inhibitor L-aminoethoxyvinylglycine. Evidence for a ketimine intermediate |journal=J. Biol. Chem. |volume=277 |issue=51 |pages=49735–42 |pmid=12228256 |doi=10.1074/jbc.M208427200 |url=|date=December 2002}}
6. ^{{cite journal |vauthors=Huai Q, Xia Y, Chen Y, Callahan B, Li N, Ke H |title=Crystal structures of 1-aminocyclopropane-1-carboxylate (ACC) synthase in complex with aminoethoxyvinylglycine and pyridoxal-5'-phosphate provide new insight into catalytic mechanisms |journal=J. Biol. Chem. |volume=276 |issue=41 |pages=38210–6 |pmid=11431475 |doi=10.1074/jbc.M103840200 |url=|date=October 2001}}
7. ^{{cite journal |vauthors=Wang KL, Li H, Ecker JR |title=Ethylene biosynthesis and signaling networks |journal=Plant Cell |volume=14 Suppl |issue= |pages=S131–51 |year=2002 |pmid=12045274 |pmc=151252 |doi= 10.1105/tpc.001768|url=}}
8. ^{{cite journal |vauthors=Yip WK, Moore T, Yang SF |title=Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=6 |pages=2475–9 |date=March 1992|pmid=1549612 |pmc=48681 |doi= 10.1073/pnas.89.6.2475|url=}}
9. ^{{cite journal |vauthors=Acaster MA, Kende H |title=Properties and Partial Purification of 1-Aminocyclopropane-1-carboxylate Synthase |journal=Plant Physiol. |volume=72 |issue=1 |pages=139–45 |date=May 1983|pmid=16662947 |pmc=1066183 |doi= 10.1104/pp.72.1.139|url=}}
10. ^{{cite journal |vauthors=Lewis DR, Negi S, Sukumar P, Muday GK |title=Ethylene inhibits lateral root development, increases IAA transport and expression of PIN3 and PIN7 auxin efflux carriers |journal=Development |volume=138 |issue=16 |pages=3485–95 |pmid=21771812 |doi=10.1242/dev.065102 |url=|date=August 2011}}
11. ^{{cite journal |vauthors=Kathiresan A, Nagarathna KC, Moloney MM, Reid DM, Chinnappa CC |title=Differential regulation of 1-aminocyclopropane-1-carboxylate synthase gene family and its role in phenotypic plasticity in Stellaria longipes |journal=Plant Mol. Biol. |volume=36 |issue=2 |pages=265–74 |pmid=9484438 |doi= 10.1023/A:1005994118535|date=January 1998}}
12. ^{{cite journal |vauthors=Yip WK, Moore T, Yang SF |title=Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=6 |pages=2475–9 |date=March 1992|pmid=1549612 |pmc=48681 |doi= 10.1073/pnas.89.6.2475|url=}}
13. ^{{cite journal |vauthors=Yip WK, Moore T, Yang SF |title=Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=6 |pages=2475–9 |date=March 1992|pmid=1549612 |pmc=48681 |doi= 10.1073/pnas.89.6.2475|url=}}
14. ^{{cite journal |vauthors=Yip WK, Moore T, Yang SF |title=Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=6 |pages=2475–9 |pmid=1549612 |pmc=48681 |doi= 10.1073/pnas.89.6.2475|url=|date=March 1992}}
15. ^{{cite journal |vauthors=Acaster MA, Kende H |title=Properties and Partial Purification of 1-Aminocyclopropane-1-carboxylate Synthase |journal=Plant Physiol. |volume=72 |issue=1 |pages=139–45 |date=May 1983|pmid=16662947 |pmc=1066183 |doi= 10.1104/pp.72.1.139|url=}}
16. ^{{cite journal |vauthors=Nakatsuka A, Murachi S, Okunishi H |title=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 |journal=Plant Physiol. |volume=118 |issue=4 |pages=1295–305 |pmid=9847103 |pmc=34745 |doi= 10.1104/pp.118.4.1295|url=|date=December 1998|display-authors=etal}}

Enzyme mechanism

Regulation

Structure

Catalytic domain

Biological function and applications

Notes

References