Structural Interactions with Enzymes

Grau, Ulrich

doi:10.1016/b978-0-12-244750-1.50014-2

Cited by 26 publications

(22 citation statements)

References 109 publications

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“…It is known from L-LDHs that the reduced coenzyme binds stronger to the protein than the oxidized one. Its higher hydrophobicity ®ts better in the cluster of non-polar side-chains found generally at the nicotinamide face opposite to the substrate (Grau, 1982). This hydrophobic environment increases the electrophilicity of the pyridinium ring in particular at the C4N atom (Oppenheimer & Handlon, 1992) and is formed by Ile105, Ile156 and Ala297 in D-HicDH (Figure 12).…”

Section: Cosubstrate Bindingmentioning

confidence: 96%

“…Such a disorder is often observed in crystal structures of lactate dehydrogenase/NAD complexes (Grau, 1982). It is known from L-LDHs that the reduced coenzyme binds stronger to the protein than the oxidized one.…”

Section: Cosubstrate Bindingmentioning

confidence: 98%

“…Interactions with the nicotinamide ribose generally contribute only marginally to the free energy of NAD binding, but nevertheless they were regarded as important for catalysis (Grau, 1982). Among these interactions in D-HicDH there are hydrogen bonds between the atom O2* of nicotinamide ribose and the guanidinium group of Arg234 (Table 6a, Figure 13).…”

Section: Cosubstrate Bindingmentioning

confidence: 99%

“…Sulphate is known to be preferentially bound to the functionally and structurally similar active sites of L-LDHs when these are crystallized with ammonium sulphate as precipitating agent (Grau, 1982). The hypothesis of a competitive binding of 2-oxoisocaproate and sulphate was supported by the subsequent re®nement calculation in which this situation was simulated.…”

Section: Electron Density At the Active Sitementioning

confidence: 99%

“…This residue, which is conserved among the sequences of Figure 2, is not only a key residue for NAD binding but also for recognition. It is responsible for the metabolically important distinction between NAD and NADP , as in the latter the negatively charged phosphate group linked to the C2 H atom prevents binding of a carboxylate side-chain (Grau, 1982).…”

Section: Cosubstrate Bindingmentioning

confidence: 99%

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Crystal structure of a ternary complex of d -2-hydroxyisocaproate dehydrogenase from Lactobacillus casei , NAD + and 2-oxoisocaproate at 1.9 Å resolution 1 1Edited by R. Huber

Dengler

Niefind

Kieß

et al. 1997

Journal of Molecular Biology

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Section: Cosubstrate Bindingmentioning

confidence: 96%

Section: Cosubstrate Bindingmentioning

confidence: 98%

Section: Cosubstrate Bindingmentioning

confidence: 99%

Section: Electron Density At the Active Sitementioning

confidence: 99%

Section: Cosubstrate Bindingmentioning

confidence: 99%

See 3 more Smart Citations

Crystal structure of a ternary complex of d -2-hydroxyisocaproate dehydrogenase from Lactobacillus casei , NAD + and 2-oxoisocaproate at 1.9 Å resolution 1 1Edited by R. Huber

Dengler

Niefind

Kieß

et al. 1997

Journal of Molecular Biology

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Unusual conformation of nicotinamide adenine dinucleotide (NAD) bound to diphtheria toxin: A comparison with NAD bound to the oxidoreductase enzymes

Bell¹,

Yeates

Eisenberg

1997

Protein Science

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The conformation of NAD bound to diphtheria toxin (DT), an ADP-ribosylating enzyme, has been compared to the conformations of NAD(P) bound to 23 distinct NAD(P)-binding oxidoreductase enzymes, whose structures are available in the Brookhaven Protein Data Bank. For the oxidoreductase enzymes, NAD(P) functions as a cofactor in electron transfer, whereas for DT, NAD is a labile substrate in which the N-glycosidic bond between the nicotinamide ring and the N-ribose is cleaved. All NAD(P) conformations were compared by (1) visual inspection of superimposed molecules, (2) RMSD of atomic positions, (3) principal component analysis, and (4) analysis of torsion angles and other conformational parameters. Whereas the majority of oxidoreductase-bound NAD(P) conformations are found to be similar, the conformation of NAD bound to DT is found to be unusual. Distinctive features of the conformation of NAD bound to DT that may be relevant to DT's function as an ADP-ribosylating enzyme include (1) an unusually short distance between the PN and NlN atoms, reflecting a highly folded conformation for the nicotinamide mononucleotide (NMN) portion of NAD, and (2) a torsion angle xN -0" about the scissile N-glycosidic bond, placing the nicotinamide ring outside of the preferred anti and syn orientations. In NAD bound to DT, the highly folded NMN conformation and torsion angle ,yN -0" could contribute to catalysis, possibly by orienting the C1 'N atom of NAD for nucleophilic attack, or by placing strain on the N-glycosidic bond, which is cleaved by DT. The unusual overall conformation of NAD bound to DT is likely to reflect the structure of DT, which is unusual among NAD(P)-binding enzymes. In DT, the NAD binding site is formed at the junction of two antiparallel P-sheets. In contrast, although the 24 oxidoreductase enzymes belong to at least six different structural classes, almost all of them bind NAD(P) at the C-terminal end of a parallel P-sheet. The structural alignments and principal component analysis show that enzymes of the same structural class bind to particularly similar conformations of NAD(P), with few exceptions. The conformation of NAD bound to DT superimposes closely with that of an NAD analogue bound to Pseudomonas exotoxin A, an ADP-ribosylating toxin that is structurally homologous to DT. This suggests that all of the ADP-ribosylating enzymes that are structurally homologous to DT and ETA will bind a highly similar conformation of NAD.

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Biologically Active Nucleosides and Nucleotides: Conformational Features and Interactions with Enzymes

Birnbaum¹,

Shugar²

1987

Topics in Nucleic Acid Structure

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Structural Interactions with Enzymes

Cited by 26 publications

References 109 publications

Crystal structure of a ternary complex of d -2-hydroxyisocaproate dehydrogenase from Lactobacillus casei , NAD + and 2-oxoisocaproate at 1.9 Å resolution 1 1Edited by R. Huber

Crystal structure of a ternary complex of d -2-hydroxyisocaproate dehydrogenase from Lactobacillus casei , NAD + and 2-oxoisocaproate at 1.9 Å resolution 1 1Edited by R. Huber

Unusual conformation of nicotinamide adenine dinucleotide (NAD) bound to diphtheria toxin: A comparison with NAD bound to the oxidoreductase enzymes

Biologically Active Nucleosides and Nucleotides: Conformational Features and Interactions with Enzymes

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