A Novel NAD-binding Protein Revealed by the Crystal Structure of 2,3-Diketo-l-gulonate Reductase (YiaK)

Forouhar, F.; Lee, Insun; Benach, J.; Kulkarni, Kaushal; Xiao, Rong; Acton, Thomas; Montelione, Gaetano T.; Tong, Liang

doi:10.1074/jbc.m313580200

Cited by 11 publications

(16 citation statements)

References 26 publications

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“…The enzyme exists as a dimer, and the subunit consists of three domains; domain I, domain II (NADPH binding domain), and domain III. The overall fold is similar to those of SLDH (5) and YiaK (9), which are the representatives of other clades in the new NAD(P)H-dependent oxidoreductase family and has NADH in preference to NADPH. The core of the NADPH binding domain consists of a predominantly antiparallel seven-stranded ␤-sheet distinct from the Rossmann fold (1) common to the conventional MDH/LDH superfamily.…”

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confidence: 56%

“…Open-Closed Conformation Change-One of the striking features of YiaK belonging to the new family of NAD(P)H-dependent oxidoreductases is the unusual overall conformational change from the closed to the open form upon binding of the substrates (9). Domains I and III move away from domain II to make the active site cavity large, resulting in the exposure of one side of the bound substrate molecule to the solvent ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recent biochemical and genetic studies have revealed that some of the gene products homologous to proteins belonging to the new MDH/LDH family catalyze reactions other than those involved in MDH or LDH activity, as exemplified by L-sulfolactate dehydrogenase (SLDH) (5), ureidoglycolate dehydrogenase (UGDH) (6), 2,3-diketo-L-gulonate reductase (YiaK) (7), and ⌬ 1 -piperideine-2-carboxylate (Pip2C)/ ⌬ 1 -pyrroline-2-carboxylate (Pyr2C) reductase (8). ThenewMDH/LDHfamilyhasnowbeenextendedtothenewNAD(P)Hdependent oxidoreductase family which contains proteins homologous to, but different in activities from, the new family of MDH/LDH proteins (5,9). An analysis of the primary sequence similarities and plausible functions of the new family of oxidoreductase proteins allowed the family proteins to be grouped into at least eight clusters (8,10).…”

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confidence: 99%

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Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

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Muramatsu

Mihara

et al. 2005

Journal of Biological Chemistry

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confidence: 56%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

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Muramatsu

Mihara

et al. 2005

Journal of Biological Chemistry

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“…The structures of the protein complexes with NAD ϩ were also analyzed, and the residues directly interacting with NAD ϩ were identified (30,31 Physiological Function of DpkA-We found lysine racemase activity in the periplasm of P. putida ATCCC12633 (data not shown). This is consistent with previous findings (32) and suggests a linkage between the catabolic pathways of L-lysine and D-lysine through the racemization of lysine (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Preference for NADPH as the Coenzyme-Recently, the crystal structures of YiaK from E. coli (30) and sulfolactate dehydrogenase from M. jannaschii (SLDH) (31) were determined. The structures of the protein complexes with NAD ϩ were also analyzed, and the residues directly interacting with NAD ϩ were identified (30,31 Physiological Function of DpkA-We found lysine racemase activity in the periplasm of P. putida ATCCC12633 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

The Putative Malate/Lactate Dehydrogenase from Pseudomonas putida Is an NADPH-dependent Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Involved in the Catabolism of d-Lysine and d-Proline

Muramatsu

Mihara

Kakutani

et al. 2005

Journal of Biological Chemistry

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A Pseudomonas putida ATCC12633 gene, dpkA, encoding a putative protein annotated as malate/L-lactate dehydrogenase in various sequence data bases was disrupted by homologous recombination. The resultant dpkA ؊ mutant was deprived of the ability to use D-lysine and also D-proline as a sole carbon source. The dpkA gene was cloned and overexpressed in Escherichia coli, and the gene product was characterized. The enzyme showed neither malate dehydrogenase nor lactate dehydrogenase activity but catalyzed the NADPH-dependent reduction of such cyclic imines as ⌬ 1 -piperideine-2-carboxylate and ⌬ 1 -pyrroline-2-carboxylate to form L-pipecolate and L-proline, respectively. NADH also served as a hydrogen donor for both substrates, although the reaction rates were less than 1% of those with NADPH. The reverse reactions were also catalyzed by the enzyme but at much lower rates. Thus, the enzyme has dual metabolic functions, and we named the enzyme ⌬ 1 -piperideine-2-carboxylate/⌬ 1 -pyrroline-2-carboxylate reductase, the first member of a novel subclass in a large family of NAD(P)-dependent oxidoreductases.Lactate dehydrogenase (LDH) 1 and malate dehydrogenase (MDH) comprise a complex protein superfamily with multiple enzyme homologs found in eubacteria, Archaea, and eukaryotes (1). They catalyze NAD(P)-dependent interconversions between lactate and pyruvate and between malate and oxaloacetate, respectively. However, a new class of NAD(P)-dependent malate/L-lactate dehydrogenases with no sequence homology to "orthodox" MDH or LDH has been demonstrated (2, 3). Moreover, they have no Rossmann fold, which is a sixstranded parallel ␤-sheet core surrounded on both sides by helices (4), in their NAD(P)-binding domains in contrast to the orthodox proteins. Consequently, the new class of malate/Llactate dehydrogenase family has been distinguished from the orthodox one as shown in protein data bases such as InterPro (www.ebi.ac.uk/interpro/index.html) (5) and Pfam (www.sanger. ac.uk/Software/Pfam/) (6). However, many of the family members are annotated without functional evidence as MDH or LDH only because of their sequence similarities to those of a few enzymes such as MDH from Methanothermus fervidus (2) and LDH from Alcaligenes eutrophus (3). In fact, three hypothetical MDHs of this family have been shown to be (S)-2-hydroxyacid dehydrogenase (7), ureidoglycolate dehydrogenase (8), and 2,3-diketo-L-gulonate reductase (9). The NAD(P) dependence is common to them, but no other functional similarities can be assigned among them. Thus, we expect the occurrence of various other proteins with new functions in this family even though they are annotated as MDH (or LDH) in protein data bases.Pseudomonas strains use both enantiomers of lysine as a sole source of carbon (as well as nitrogen) (10, 11). L-Lysine is catabolized by Pseudomonas putida through the ␦-aminovalerate pathway (11), whereas D-lysine is catabolized through the pipecolate pathway involving a series of reactions through six-carbon cyclic intermediates (12, 13) (Fig. 1)...

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Functional insights from structural genomics

Forouhar

Kuzin

Seetharaman

et al. 2007

J Struct Funct Genomics

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Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNA methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF_0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP_1951), and a 12-stranded beta-barrel with a novel fold (V. parahaemolyticus VPA1032).

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A Novel NAD-binding Protein Revealed by the Crystal Structure of 2,3-Diketo-l-gulonate Reductase (YiaK)

Cited by 11 publications

References 26 publications

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

The Putative Malate/Lactate Dehydrogenase from Pseudomonas putida Is an NADPH-dependent Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Involved in the Catabolism of d-Lysine and d-Proline

Functional insights from structural genomics

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