Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme

Barbosa, J.A.R.G.; Smith, Brian J.; DeGori, R.; Ooi, Hua Chee; Marcuccio, Sebastian M.; Campi, Eva M.; Jackson, W. Roy; Brossmer, Reinhard; Sommer, Monika; Lawrence, Michael C.

doi:10.1006/jmbi.2000.4138

Cited by 79 publications

(123 citation statements)

References 35 publications

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“…From the structural point of view a ring opening before this Schiff base formation, which is discussed in the literature [8], seems not to be a prerequisite for the start of the lyase reaction and thus the model developed by Barbosa et al (2000) is confirmed [45]. Furthermore, the pH optimum of the lyase is above 7, which is not in favour of protonation of the whole molecule.…”

Section: Sialate-lyasementioning

confidence: 95%

“…The ab initio calculations are in favour of such a reaction. Since C(2) is rather positive (0.6), C(3) nearly neutral and C(4) also positive (0.3), in combination with the OH-group (-0.3) of C(4), these atoms are properly lined for interactions with the lyase, where a lysine is known to start the reaction by a nucleophilic attack at C(2) [44,45].…”

Section: Sialate-lyasementioning

confidence: 99%

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Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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This study presents ab initio calculations on six sialic acid derivatives (N-acetylneuraminic acid, 2-deoxy-2,3-didehydro-Nacetylneuraminic acid, N-acetyl-4-O-acetylneuraminic acid, N-glycolylneuraminic acid, N-glycolyl-4-O-acetylneuraminic acid and N-acetyl-9-O-acetylneuraminic acid). The calculations were carried out using the GAMESS-UK-Program. Since the charge distribution of a ligand has an essential impact on the specific interaction with an enzyme or a receptor, the precise results of ab initio calculations lead to significant information concerning possible roles of the different functional groups occurring on sialic acids. In correlation to this, valuable conclusions about the activities of different sialic acid-specific enzymes, such as sialidases, trans-sialidases, lyases and O-acetyl-or O-methyltransferases can be drawn, since these activities strongly depend on the presence or absence of the various functional groups. q 2004 Published by Elsevier B.V.

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Section: Sialate-lyasementioning

confidence: 95%

Section: Sialate-lyasementioning

confidence: 99%

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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“…Sialic acid aldolases or N-acetylneuraminate lyases (EC 4.1.3.3,NanA) are type I aldolases that catalyze the reversible aldol cleavage of N-acetylneuraminic acid (Neu5Ac) to form pyruvate and N-acetyl-D-mannosamine (ManNAc) with the equilibrium favoring the Neu5Ac cleavage (Reaction 1) (Barbosa et al 2000;Comb and Roseman 1960;Deijl and Vliegenthart 1983;Wong and Whitesides 1994).…”

Section: Introductionmentioning

confidence: 99%

Pasteurella multocida sialic acid aldolase: a promising biocatalyst

Cao

et al. 2008

Appl Microbiol Biotechnol

113

151

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Sialic acid aldolases or N-acetylneuraminate lyases (NanAs) catalyze the reversible aldol cleavage of N-acetylneuraminic acid (Neu5Ac) to form pyruvate and N-acetyl-D-mannosamine (ManNAc). A capillary electrophoresis (CE) assay was developed to directly characterize the activities of NanAs in both Neu5Ac cleavage and Neu5Ac synthesis directions. The assay was used to obtain the pH profile and the kinetic data of a NanA cloned from Pasteurella multocida P-1059 (PmNanA) and a previously reported recombinant Escherichia coli K12 NanA (EcNanA). Both enzymes are active in a broad pH range of 6.0-9.0 in both reaction directions and have similar kinetic parameters. Substrates specificity studies showed that 5-O-methyl-ManNAc, a ManNAc derivative, can be used efficiently as a substrate by PmNanA, but not efficiently by EcNanA, for the synthesis of 8-O-methyl Neu5Ac. In addition, PmNanA (250 mg per liter culture) has a higher expression level (2.5 fold) than EcNanA (94 mg per liter culture). The higher expression level and a broader substrate tolerance make PmNanA a better catalyst than EcNanA for the chemoenzymatic synthesis of sialic acids and their derivatives.

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“…A tyrosine residue in the substrate binding pocket is also completely conserved and is predicted to be involved directly in the reaction mechanism or to function in stabilizing the position of the lysine (47,48). The similarities of the sequences of HypD and LhpC to those of the other characterized members of this group and the fact that both have the conserved active-site lysine and tyrosine residues (see Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The proposed mechanism for the NAL subfamily is the formation of a covalent Schiff base intermediate between the nitrogen of the active-site lysine side chain and substrate. However, the reactions catalyzed vary, depending on the enzyme, and include aldol cleavage, condensation, and decarboxylation (47,48). Addition of HypD and LhpC to the subfamily adds deamination to the reactions performed by this group of proteins (12; this study).…”

Section: Discussionmentioning

confidence: 96%

l-Hydroxyproline andd-Proline Catabolism in Sinorhizobium meliloti

et al. 2016

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Sinorhizobium meliloti IMPORTANCEHydroxyproline is abundant in proteins in animal and plant tissues and serves as a carbon and a nitrogen source for bacteria in diverse environments, including the rhizosphere, compost, and the mammalian gut. While the main biochemical features of bacterial hydroxyproline catabolism were elucidated in the 1960s, the genetic and molecular details have only recently been determined. Elucidating the genetics of hydroxyproline catabolism will aid in the annotation of these genes in other genomes and metagenomic libraries. This will facilitate an improved understanding of the importance of this pathway and may assist in determining the prevalence of hydroxyproline in a particular environment.4-Hydroxyproline and 3-hydroxyproline in animal and plant proteins are formed through the posttranslational modification of proline residues by the enzyme proline hydroxylase. In some bacteria, hydroxyproline is synthesized from free L-proline, where it is employed in the synthesis of secondary metabolites (1, 2). 4-Hydroxyproline has two chiral carbon atoms, and of its four isomeric forms, trans-4-hydroxy-L-proline (trans-4-L-Hyp) and cis-4-hydroxy-D-proline (cis-4-D-Hyp) appear to be the two most common isomers. trans-4-

show abstract

Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme

Cited by 79 publications

References 35 publications

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Pasteurella multocida sialic acid aldolase: a promising biocatalyst

l-Hydroxyproline andd-Proline Catabolism in Sinorhizobium meliloti

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