Acetolactate synthase
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Acetolactate_synthase".

Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase complexed with a sulfonylurea herbicide, metsulfuron-methyl.1
ilvB (bacterial acetolactate synthase)-like
Identifiers
Symbol	ILVBL
Entrez	10994
HUGO	6041
OMIM	605770
RefSeq	NM_176826
UniProt	Q99651
Other data
EC number	2.2.1.6
Locus	Chr. 19 p13.1

The acetolactate synthase (ALS) enzyme (also known as acetohydroxy acid synthase, or AHAS) is a protein which in humans is encoded by the ILVBL gene.² ALS catalyzes the first step in the synthesis of the branched-chain amino acids (valine, leucine, and isoleucine).³

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.

Function

This certain proteins is an enzyme involving catalytic activity, more specifically, a part of the biosynthesis of various amino acids. This enzyme has the Enzyme Commission Code is 2.2.1.6. This is broken down into the enzyme being 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.⁴

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.

The primary sequence is listed below. Residues involved in catalytic activity are bolded.

TFISRFAPDQPRKGADILVEALERQGVETVFAYPGGASMEIHQALTRSSSIRNVLPRHEQGGVFAAEGYARSSGKPGICIATSGPGATNLVSGLADALLD

SVPLVAITGQVPRRMIGTDAFQETPIVEVTRSITKHNYLVMDVEDIPRIIEEAFFLATSGRPGPVLVDVPKDIQQQLAIPNWEQAMRLPGYMSRMPKPPE

DSHLEQIVRLISESKKPVLYVGGGCLNSSDELGRFVELTGIPVASTLMGLGSYPXDDELSLHMLGMHGTVYANYAVEHSDLLLAFGVRFDDRVTGKLEAF

ASRAKIVHIDIDSAEIGKNKTPHVSVCGDVKLALQGMNKVLENRAEELKLDFGVWRNELNVQKQKFPLSFKTFGEAIPPQYAIKVLDELTDGKAIISTGV

GQHQMWAAQFYNYKKPRQWLSSGGLGAMGFGLPAAIGASVANPDAIVVDIDGDGSFIMNVQELATIRVENLPVKVLLLNNQHLGMVMQWEDRFYKANRAH

TFLGDPAQEDEIFPNMLLFAAACGIPAARVTKKADLREAIQTMLDTPGPYLLDVICPHQEHVLPMIPSGGTFNDVITEGDGR

Inhibitors

Inhibitors of ALS are used as herbicides that slowly starve affected plants of these amino acids, which eventually leads to inhibition of DNA synthesis. They affect grasses and dicots alike. The ALS inhibitor family includes sulfonylureas (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 catalysis, 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).

References

External links

• MeSH Acetolactate+synthase
• Ramashandran Plot[1]
• [2]

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