4-Hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7, dihydrodipicolinate synthase, dihydropicolinate synthetase, dihydrodipicolinic acid synthase,
L-aspartate-4-semialdehyde hydro-lyase (adding pyruvate and cyclizing), ''dapA (gene)'') is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
with the
systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivial ...
L-aspartate-4-semialdehyde hydro-lyase (adding pyruvate and cyclizing; (4''S'')-4-hydroxy-2,3,4,5-tetrahydro-(2''S'')-dipicolinate-forming).
This enzyme
catalyses the following
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking ...
:
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic a ...
+
L-aspartate-4-semialdehyde
(2''S'',4''S'')-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H
2O
The reaction proceeds in three consecutive steps.
Function
This enzyme belongs to the family of
lyase
In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bonds by means other than hydrolysis (a substitution reaction) and oxidation, often forming a new double bond or a new ring structu ...
s, specifically the amine-lyases, which cleave carbon-nitrogen bonds. 4-hydroxy-tetrahydrodipicolinate synthase is the key
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
in
lysine biosynthesis
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −CO ...
via the diaminopimelate pathway of
prokaryotes
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...
, some
phycomycetes
Phycomycetes is an obsolete polyphyletic taxon for certain fungi with aseptate hyphae. It is used in the Engler system. Asexual reproduction takes place by zoospores(motile) or by Aplanospores(non-motile).These spores are endogenously produced in ...
, and
higher plants
Vascular plants (), also called tracheophytes () or collectively Tracheophyta (), form a large group of land plants ( accepted known species) that have lignified tissues (the xylem) for conducting water and minerals throughout the plant. They al ...
. The enzyme
catalyses the condensation of L-aspartate-beta-semialdehyde and pyruvate to 4-hydroxy-tetrahydropicolinic acid via a
ping-pong mechanism
Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in th ...
in which
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic a ...
binds to the enzyme by forming a
Schiff base with a
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...
residue.
Related enzymes
Three other
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s are
structurally related to this enzyme and probably also act via a similar catalytic mechanism. These are ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
''
N-acetylneuraminate lyase
The enzyme ''N''-acetylneuraminate lyase () catalyzes the chemical reaction
:''N''-acetylneuraminate \rightleftharpoons N-acetyl-D-mannosamine + pyruvate
This enzyme belongs to the family of lyases, specifically the oxo-acid-lyases, which cleave ...
() (protein NanA), which
catalyses the condensation of ''N''-acetyl-D-mannosamine and pyruvate to form
''N''-acetylneuraminate; ''
Rhizobium meliloti
''Ensifer meliloti'' (formerly ''Rhizobium meliloti'' and ''Sinorhizobium meliloti'') are an aerobic, Gram-negative, and diazotrophic species of bacteria. ''S. meliloti'' are motile and possess a cluster of peritrichous flagella. ''S. meliloti'' ...
'' (''Sinorhizobium meliloti'') protein MosA,
which is involved in the biosynthesis of the rhizopine 3-''O''-methyl-scyllo-inosamine; and ''E. coli'' hypothetical protein YjhH.
Structure
The
sequence
In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is called ...
s of 4-hydroxy-tetrahydrodipicolinate synthase from different sources are well-conserved. The structure takes the form of a homotetramer, in which 2
monomer
In chemistry, a monomer ( ; '' mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
...
s are related by an approximate 2-fold
symmetry
Symmetry (from grc, συμμετρία "agreement in dimensions, due proportion, arrangement") in everyday language refers to a sense of harmonious and beautiful proportion and balance. In mathematics, "symmetry" has a more precise definiti ...
.
Each monomer comprises 2 domains: an 8-fold α/β-barrel, and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
α-helical domain. The
fold resembles that of ''N''-acetylneuraminate lyase. The
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate ( binding site) ...
lysine is located in the barrel domain, and has access via 2 channels on the C-terminal side of the barrel.
References
Further reading
*
External links
*
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EC 4.3.3
Enzymes of known structure
Protein domains