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 with the
systematic name 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
:
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 aci ...
+
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 structure. ...
s, specifically the amine-lyases, which cleave carbon-nitrogen bonds. 4-hydroxy-tetrahydrodipicolinate synthase is the key
enzyme 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 & Connec ...
, 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 i ...
, and
higher plants. 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 t ...
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 aci ...
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 −C ...
residue.
Related enzymes
Three other
proteins are
structurally related to this enzyme and probably also act via a similar catalytic mechanism. These are ''
Escherichia coli''
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
sequences of 4-hydroxy-tetrahydrodipicolinate synthase from different sources are well-conserved. The structure takes the form of a homotetramer, in which 2
monomers 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 definit ...
.
Each monomer comprises 2 domains: an 8-fold α/β-barrel, and a
C-terminal α-helical domain. The
fold
Fold, folding or foldable may refer to:
Arts, entertainment, and media
* ''Fold'' (album), the debut release by Australian rock band Epicure
*Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot
*Above ...
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) a ...
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
*
{{Portal bar, Biology, border=no
EC 4.3.3
Enzymes of known structure
Protein domains