1pu2
From Proteopedia
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Crystal Structure of the K246R Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae
Overview
The reversible dephosphorylation of beta-aspartyl phosphate to, L-aspartate-beta-semialdehyde (ASA) in the aspartate biosynthetic pathway, is catalyzed by aspartate-beta-semialdehyde dehydrogenase (ASADH). The, product of this reaction is a key intermediate in the biosynthesis of, diaminopimelic acid, an integral component of bacterial cell walls and a, metabolic precursor of lysine and also a precursor in the biosynthesis of, threonine, isoleucine and methionine. The structures of selected, Haemophilus influenzae ASADH mutants were determined in order to evaluate, the residues that are proposed to interact with the substrates ASA or, phosphate. The substrate Km values are not altered by replacement of, either an active-site arginine (Arg270) with a lysine or a putative, phosphate-binding group (Lys246) with an arginine. However, the, interaction of phosphate with the enzyme is adversely affected by, replacement of Arg103 with lysine and is significantly altered when a, neutral leucine is substituted at this position. A conservative Glu243 to, aspartate mutant does not alter either ASA or phosphate binding, but, instead results in an eightfold increase in the Km for the coenzyme NADP., Each of the mutations is shown to cause specific subtle active-site, structural alterations and each of these changes results in decreases in, catalytic efficiency ranging from significant (approximately 3% native, activity) to substantial (<0.1% native activity).
About this Structure
1PU2 is a Single protein structure of sequence from Haemophilus influenzae. Active as Aspartate-semialdehyde dehydrogenase, with EC number 1.2.1.11 Full crystallographic information is available from OCA.
Reference
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase., Blanco J, Moore RA, Faehnle CR, Coe DM, Viola RE, Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1388-95. Epub 2004, Jul 21. PMID:15272161
Page seeded by OCA on Wed Nov 21 00:07:33 2007
