Acetolactate synthase
Encyclopedia
The acetolactate synthase (ALS) enzyme
(also known as acetohydroxy acid synthase, or AHAS) is a protein
found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids
(valine
, leucine
, and isoleucine
).
It is a human protein of yet unknown function, sharing some sequence similarity with bacterial ALS, and is encoded by the ILVBL gene
.
The structure of acetolactate synthase that was used for the picture on this page was determined using X-ray diffraction at 2.70 angstroms. X-ray diffraction uses X-rays at specified wavelengths to produce patterns, as the X–ray is scattered in certain ways that give an idea to the structure of the molecule being analyzed.
There are five specific ligands that interact with this protein. The five are listed below.
This enzyme is the first of several enzymes in the biosynthesis cycle for leucine and valine, taking the initial pyruvate molecules and starting the conversion from pryuvic acid to the amino acids. The specific residue that is responsible for this is a glycine at position 511 in the protein. This is the one that requires a cofactor of TPP for its function.
There are four specific residues that are responsible for catalytic activity in this enzyme. They are listed here with cofactors required written after.
The primary sequence is listed below. Residues involved in catalytic activity are bolded.
of ALS are used as herbicides that slowly starve affected plants of these amino acid
s, which eventually leads to inhibition of DNA synthesis. They affect grasses and dicots alike. The ALS inhibitor family includes sulfonylurea
s (SUs), imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidinyl oxybenzoates (POBs), and sulfonylamino carbonyl triazolinones (SCTs).
, and a small subunit for feedback inhibition. Each subunit pair is located on its own operon
. Together, these operons code for several enzymes involved in branched-chain amino acid biosynthesis. Regulation is different for each operon.
The ilvGMEDA operon (encoding ALS II, branched-chain-amino-acid transaminase, dihydroxy-acid dehydratase
, and threonine ammonia-lyase
) is regulated by feedback inhibition in the form of transcriptional attenuation. That is, transcription is reduced in the presence of the pathway's end-products, the branched-chain amino acids.
The ilvBNC operon, which encodes ALS I and a ketol-acid reductoisomerase
, is similarly regulated, but is specific to isoleucine and leucine; valine does not affect it directly.
Both the ilvGMEDA and ilvBNC operons are derepressed during shortages of the branched-chain amino acids by the same mechanism that represses them. Both of these operons as well as the third, ilvIH, are regulated by leucine-responsive protein
(Lrp).
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
(also known as acetohydroxy acid synthase, or AHAS) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids
Branched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
(valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
, leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
).
It is a human protein of yet unknown function, sharing some sequence similarity with bacterial ALS, and is encoded by the ILVBL gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Structure
Acetolactase is a protein consisting of 590 residues. These residues are classified into three separate subunits. The units are d1yhya1, d1yhya2 ,and d1yhya3. This is classified by the SCOP domain assignments.The structure of acetolactate synthase that was used for the picture on this page was determined using X-ray diffraction at 2.70 angstroms. X-ray diffraction uses X-rays at specified wavelengths to produce patterns, as the X–ray is scattered in certain ways that give an idea to the structure of the molecule being analyzed.
There are five specific ligands that interact with this protein. The five are listed below.
| Ligand Identifier | Name | Structure |
|---|---|---|
| P22 | ETHYL DIHYDROGEN DIPHOSPHATE | C2H8O7P2 |
| NHE | 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID | C8H17NO3S |
| Mg | Magnesium Ion | Mg |
| FAD | FLAVIN-ADENINE DINUCLEOTIDE | C27H33N9O15P2 |
| 1SM | METHYL 2-[({[(4,6-DIMETHYLPYRIMIDIN-2-YL)AMINO]CARBONYL}AMINO)SULFONYL]BENZOATE | C15H16N4O5 S |
Function
This certain protein is an enzyme involving catalytic activity, to be more specific, a part of the biosynthesis of various amino acids. This enzyme has the Enzyme Commission Code is 2.2.1.6, which means that the enzyme is a transketolase or a transaldolase, which is classified under the transferases that transfer aldehyde or ketone residues. In this case, acetolactase synthase is a transketolase, which moves back and forth, having both catabolic and anabolic forms. These act on a ketone (pyruvate) and can go back and forth in the metabolic chain. These are found in humans, animals, plants, and bacteria. In plants, they are located in the chloroplasts in order to help with the metabolic processes. In several experiments, it has been shown that mutated strands of Escherichia coli K-12 without the enzyme were not able to grow in the presence of only acetate or oleate as the only carbon sources.Catalytic activity
Acetolactate synthesis, also known as acetohydroxy acid synthase, is an enzyme specifically involved in the chemical reaction involving the conversion of two pyruvate molecules to an acetolactate molecule and carbon dioxide. The reaction uses thyamine pyrophosphate in order to link the two pyruvate molecules. The resulting product of this reaction, acetolactate, eventually becomes valine, leucine, and isoleucine. All three of these amino acids are essential amino acids and cannot be synthesized in the organism.- 2 CH3COCOO– →(acetolactate synthase)→ CH3COCOHCH3COO– + CO2
This enzyme is the first of several enzymes in the biosynthesis cycle for leucine and valine, taking the initial pyruvate molecules and starting the conversion from pryuvic acid to the amino acids. The specific residue that is responsible for this is a glycine at position 511 in the protein. This is the one that requires a cofactor of TPP for its function.
There are four specific residues that are responsible for catalytic activity in this enzyme. They are listed here with cofactors required written after.
| Residue | Position | Cofactors |
|---|---|---|
| Valine | 485 | HE3 |
| Methiodine | 513 | HE3 |
| Histidine | 643 | - |
| Glycine | 511 | TPP |
The primary sequence is listed below. Residues involved in catalytic activity are bolded.
Inhibitors
InhibitorsEnzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of ALS are used as herbicides that slowly starve affected plants of these amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, which eventually leads to inhibition of DNA synthesis. They affect grasses and dicots alike. The ALS inhibitor family includes sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
s (SUs), imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidinyl oxybenzoates (POBs), and sulfonylamino carbonyl triazolinones (SCTs).
Regulation
Acetolactate synthase consists of three pairs of subunits. Each pair includes a large subunit, which is thought to be responsible for catalysisCatalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
, and a small subunit for feedback inhibition. Each subunit pair is located on its own operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
. Together, these operons code for several enzymes involved in branched-chain amino acid biosynthesis. Regulation is different for each operon.
The ilvGMEDA operon (encoding ALS II, branched-chain-amino-acid transaminase, dihydroxy-acid dehydratase
Dihydroxy-acid dehydratase
In enzymology, a dihydroxy-acid dehydratase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, 2,3-dihydroxy-3-methylbutanoate, and two products, 3-methyl-2-oxobutanoate and H2O....
, and threonine ammonia-lyase
Threonine ammonia-lyase
In enzymology, a threonine ammonia-lyase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, L-threonine, and two products, Alpha-Ketobutyric_acid and NH3....
) is regulated by feedback inhibition in the form of transcriptional attenuation. That is, transcription is reduced in the presence of the pathway's end-products, the branched-chain amino acids.
The ilvBNC operon, which encodes ALS I and a ketol-acid reductoisomerase
Ketol-acid reductoisomerase
In enzymology, a ketol-acid reductoisomerase is an enzyme that catalyzes the chemical reaction-2,3-dihydroxy-3-methylbutanoate + NADP+ \rightleftharpoons -2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+...
, is similarly regulated, but is specific to isoleucine and leucine; valine does not affect it directly.
Both the ilvGMEDA and ilvBNC operons are derepressed during shortages of the branched-chain amino acids by the same mechanism that represses them. Both of these operons as well as the third, ilvIH, are regulated by leucine-responsive protein
Leucine-responsive protein
Leucine responsive protein, or Lrp, is a global regulator protein, meaning that it regulates the biosynthesis of leucine, as well as the other branched-chain amino acids, valine and isoleucine. In bacteria, it is encoded by the lrp gene....
(Lrp).
External links
- Ramachandran plotRamachandran plot-Introduction and early history:A Ramachandran plot , originally developed in 1963 by G. N. Ramachandran C. Ramakrishnan and V...
http://www.rcsb.org/pdb/images/1YHY_ram_m_500.pdf - http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/CSA/CSA_Site_Wrapper.pl?pdb=1YHY