Control of pyridoxal phosphate enzyme reaction specificity studied with .alpha.-dialkylamino acid transaminase

Bailey, Gordon B.; Chotamangsa, Orathai; Vuttivej, Kreurvul

doi:10.1021/bi00818a018

Cited by 41 publications

(27 citation statements)

References 4 publications

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“…These results suggest that a carbon chain corresponding to o-form in an a-dialkyl-aamino acid molecule is required for the enzyme action. This is consistent with the experiment 3 ) of Bailey et at.. , in which they used an enzyme catalyzing decarboxylation of o-alanine but not L-alanine. In present experiment (Table I), o-alanine was decarboxylated more rapidly by AlB decomposing enzyme than L-alanine.…”

Section: Induction Of Alb Decomposing Enzymesupporting

confidence: 90%

Aminotransferase Activity of α-Aminoisobutyric Acid Decomposing Enzyme

Honma

Ikeda

Shimomura

1972

Agricultural and Biological Chemistry

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Section: Induction Of Alb Decomposing Enzymesupporting

confidence: 90%

Aminotransferase Activity of α-Aminoisobutyric Acid Decomposing Enzyme

Honma

Ikeda

Shimomura

1972

Agricultural and Biological Chemistry

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“…Radically different results are obtained for transamination. L-Alanine is rapidly transaminated by DGD, whereas no transamination of D-alanine is detectable (15).…”

Section: Discussionmentioning

confidence: 95%

Reactions of Alternate Substrates Demonstrate Stereoelectronic Control of Reactivity in Dialkylglycine Decarboxylase

1998

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Kinetic and product analyses of the reactions of dialkylglycine decarboxylase with several alternative substrates are presented. Rate constants for the reactions of amino and keto acids of several substrates decrease logarithmically with increasing side-chain size. Conversely, k cat for L-amino acid decarboxylation increases with side-chain size. These and other data confirm a proposed model for three binding subsites in the active site. In this model, bond making and breaking in both the decarboxylation and transamination half-reactions occurs at the "A" subsite, which maintains the scissile bond aligned with the p orbitals of the conjugated aldimine and thus maximizes stereoelectronic effects. This strongly supports the proposal by Dunathan (Proc. Natl. Acad. Sci. U.S.A. 55,[712][713][714][715][716]) that PLP-dependent enzymes can largely control reaction specificity by specific orientation about C R in the external aldimine intermediate. The "B" subsite can accept either an alkyl or a carboxylate group, while the "C" subsite accepts only small alkyl groups. This model predicts the existence of nonproductive binding modes for amino acids, which is proposed to be the ultimate origin of the k cat increase with side-chain size for L-amino acid decarboxylation. The specificity of the 2-aminoisobutyrate decarboxylation half-reaction toward oxidative decarboxylation is very high (<1 in 10 5 turnovers yields nonoxidative decarboxylation). The origin of this specificity is explored with the reactions of amino-and methylaminomalonate. These substrates exhibit high yields of nonoxidative decarboxylation, providing support for a model in which the interaction between a carboxylate group in the B subsite and Arg406 is a prerequisite to proton donation to and removal from C R .Dialkylglycine decarboxylase (DGD) 1,2 from Pseudomonas cepacia is a PLP dependent enzyme that catalyzes the oxidative decarboxylation of 2,2-dialkylglycines, yielding CO 2 , a ketone, and the PMP form of the enzyme (Scheme 1). The catalytic cycle is completed by transamination of an R-keto acid, preferentially pyruvate (1-3). The overall reaction catalyzed by DGD is shown below. The unusual ability of DGD to catalyze rapidly two classical PLPdependent reactions has rekindled an interest in this enzyme.The X-ray structure of DGD has been determined to 2.1-Å resolution (4, 5). The fold of the enzyme is roughly similar to the well-studied aspartate aminotransferase (6), which is a member of evolutionary subgroup I of aminotransferases (7). DGD is a representative member of evolutionary subgroup II (8), and its fold is closely similar to the other known structures of subgroup II enzymes (9, 10). The active site structure of DGD is similar to that of aspartate aminotransferase in that the interactions made between coenzyme and protein are highly conserved (5).Toney et al. (5) proposed a structurally based model of the active site of DGD in which there are three binding subsites (A-C) that differ in their functional group specificities. One of t...

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“…Since the added proton at Ci, has pro S symmetry, it follows that the 'si' face of Cb, shown is in fact the exposed face. This is the side that is protonated (and thus we assume 'exposed') in each of the three cases already known [2][3][4] . As argued in reference [ 131 bond making and breaking at C, (or Ck) should take place in a plane perpendicular to the plane of the cofactor pi system.…”

Section: Discussionmentioning

confidence: 99%