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PDBsum entry 1b4e
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of 5-Aminolevulinic acid dehydratase from escherichia coli complexed with the inhibitor levulinic acid at 2.0 a resolution.
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Authors
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P.T.Erskine,
E.Norton,
J.B.Cooper,
R.Lambert,
A.Coker,
G.Lewis,
P.Spencer,
M.Sarwar,
S.P.Wood,
M.J.Warren,
P.M.Shoolingin-Jordan.
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Ref.
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Biochemistry, 1999,
38,
4266-4276.
[DOI no: ]
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PubMed id
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Abstract
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5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole
biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to
form the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a
homo-octameric structure with 422 symmetry in which each subunit adopts the TIM
barrel fold with a 30-residue N-terminal arm. Pairs of monomers associate with
their arms wrapped around each other. Four of these dimers interact, principally
via their arm regions, to form octamers in which each active site is located on
the surface. The active site contains two lysine residues (195 and 247), one of
which (Lys 247) forms a Schiff base link with the bound substrate analogue,
levulinic acid. Of the two substrate binding sites (referred to as A and P), our
analysis defines the residues forming the P-site, which is where the first ALA
molecule to associate with the enzyme binds. The carboxyl group of the levulinic
acid moiety forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In
proximity to the levulinic acid is a zinc binding site formed by three cysteines
(Cys 120, 122, and 130) and a solvent molecule. We infer that the second
substrate binding site (or A-site) is located between the triple-cysteine zinc
site and the bound levulinic acid moiety. Two invariant arginine residues in a
loop covering the active site (Arg 205 and Arg 216) appear to be appropriately
placed to bind the carboxylate of the A-site substrate. Another metal binding
site, close to the active site flap, in which a putative zinc ion is coordinated
by a carboxyl and five solvent molecules may account for the activating
properties of magnesium ions.
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