The Crystal Structure of β-Alanine Synthase from Drosophila melanogaster Reveals a Homooctameric Helical Turn-Like Assembly

Lundgren, Stina; Lohkamp, Bernhard; Andersen, B. N.; Piškur, Jure; Dobritzsch, Doreen

doi:10.1016/j.jmb.2008.02.011

Cited by 36 publications

(57 citation statements)

References 61 publications

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“…Other proteins found by the EMBL-EBI server are: a pyrimidine degrading enzyme from Drosophila melanogaster (r.m.s.d. 1.42 Å, 2vhh, (Lundgren et al, 2008), Nit3 protein from Saccharomyces cerevisiae (r.m.s.d. 1.61 Å, 1f89, (Kumaran et al, 2003), aliphatic amidase from Pseudomonas aeruginosa (r.m.s.d.…”

Section: Homologous Structuresmentioning

confidence: 99%

Crystallographic analysis of a thermoactive nitrilase

Raczynska

Vorgias

Antranikian

et al. 2011

Journal of Structural Biology

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Section: Homologous Structuresmentioning

confidence: 99%

Crystallographic analysis of a thermoactive nitrilase

Raczynska

Vorgias

Antranikian

et al. 2011

Journal of Structural Biology

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“…The closest known structural relative of human βUP is found in Drosophila melanogaster (DmβUP) (Lundgren et al 2008), sharing 63 % amino acid sequence identity. In solution, DmβUP exists as a mixture of oligomers but crystallizes as a homooctamer.…”

Section: Introductionmentioning

confidence: 99%

Clinical, biochemical and molecular analysis of 13 Japanese patients with β‐ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation

Nakajima

Meijer

Dobritzsch

et al. 2014

J of Inher Metab Disea

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β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant βUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, βUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human βUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that βUP deficiency is not as rare as generally considered and screening for βUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-014-9682-y) contains supplementary material, which is available to authorized users.

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“…The absence of the hydroxyl group in the Y191F mutant might decrease (but not completely eliminate) the electrophilic character of the carboxyl moiety of Glu140, resulting in a lower activity of the enzyme. [3]), hypothetical protein PH0642 (1J31; dark blue [45]), YLR351C (1F89; red [27]), NIT (fragile histidine nitrilase triad fusion protein) (1EMS; brown [41]), ␤-alanine synthase (2VHI; lemon [33]), D-carbamoylase (2GGL; magenta [12]), hydrolase (2E11; sky blue [11] …”

Section: Resultsmentioning

confidence: 99%

Biochemical and Mutational Studies of the Bacillus cereus CECT 5050T Formamidase Support the Existence of a C-E-E-K Tetrad in Several Members of the Nitrilase Superfamily

Soriano-Maldonado

Martínez-Gómez

Andújar‐Sánchez

et al. 2011

Appl Environ Microbiol

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Formamidases (EC 3.5.1.49) are poorly characterized proteins. In spite of this scarce knowledge, ammonia has been described as playing a central role in the pathogenesis of human pathogens such as Helicobacter pylori, for which formamidase has been shown to participate in the nitrogen metabolic pathway. Sequence analysis has revealed that at least two different groups of formamidases are classified as EC 3.5.1.49: on the one hand, the derivatives of the FmdA-AmdA superfamily, which are the best studied to date, and on the other hand, the derivatives of Helicobacter pylori AmiF. Here we present the cloning, purification, and characterization of a recombinant formamidase from Bacillus cereus CECT 5050T (BceAmiF), the second member of the AmiF subfamily to be characterized, showing new features of the enzyme further supporting its relationship with aliphatic amidases. We also present homology modeling-based mutational studies confirming the importance of the Glu140 and Tyr191 residues in the enzymatic activities of the AmiF family. Moreover, we can conclude that a second glutamate residue is critical in several members of the nitrilase superfamily, meaning that what has consistently been identified as a C-E-K triad is in fact a C-E-E-K tetrad.

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The Crystal Structure of β-Alanine Synthase from Drosophila melanogaster Reveals a Homooctameric Helical Turn-Like Assembly

Cited by 36 publications

References 61 publications

Crystallographic analysis of a thermoactive nitrilase

Crystallographic analysis of a thermoactive nitrilase

Clinical, biochemical and molecular analysis of 13 Japanese patients with β‐ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation

Biochemical and Mutational Studies of the Bacillus cereus CECT 5050T Formamidase Support the Existence of a C-E-E-K Tetrad in Several Members of the Nitrilase Superfamily

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