Structure, evolution and action of vitamin B6-dependent enzymes

Jansonius, Johan N.

doi:10.1016/s0959-440x(98)80096-1

Cited by 393 publications

(283 citation statements)

References 53 publications

Supporting

Mentioning

277

Contrasting

Order By: Relevance

“…Unlike CcbF, an oxo group of the peroxo intermediate at the ␣C atom is retained, which can be readily explained by standard PLP chemistry, including proton abstraction at the ␣C atom and electron shuffling (Fig. 7B) (25). This would permit the direct formation of the amide of the decarboxylated amino acid, which would be to our knowledge the first description of such a reaction.…”

Section: Functional Role Of Pvdnmentioning

confidence: 99%

See 1 more Smart Citation

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

Ringel

Dräger

Brüser

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by F. Peter GuengerichPyoverdines are high affinity siderophores produced by a broad range of pseudomonads to enhance growth under iron deficiency. They are especially relevant for pathogenic and mutualistic strains that inhabit iron-limited environments. Pyoverdines are generated from non-ribosomally synthesized highly modified peptides. They all contain an aromatic chromophore that is formed in the periplasm by intramolecular cyclization steps. Although the cytoplasmic peptide synthesis and side-chain modifications are well characterized, the periplasmic maturation steps are far from understood. Out of five periplasmic enzymes, PvdM, PvdN, PvdO, PvdP, and PvdQ, functions have been attributed only to PvdP and PvdQ. The other three enzymes are also regarded as essential for siderophore biosynthesis. The structure of PvdN has been solved recently, but no function could be assigned. Here we present the first in-frame deletion of the PvdN-encoding gene. Unexpectedly, PvdN turned out to be required for a specific modification of pyoverdine, whereas the overall amount of fluorescent pyoverdines was not altered by the mutation. The mutant strain grew normally under iron-limiting conditions. Mass spectrometry identified the PvdN-dependent modification as a transformation of the N-terminal glutamic acid to a succinamide. We postulate a pathway for this transformation catalyzed by the enzyme PvdN, which is most likely functional in the case of all pyoverdines.Under aerobic conditions in the neutral pH range, iron can form insoluble Fe III oxide hydrates, limiting the amount of readily available iron. Therefore, many organisms produce siderophores that bind and thereby solubilize iron in their surroundings. A special group of these siderophores are the pyoverdines, yellow-green pigments that were first described in 1892 by Gessard (1). Turfitt (2, 3) used the production of pyoverdines for taxonomic classification of "fluorescent pseudomonads," which include many important pathogenic as well as beneficial pseudomonads. Today it is known that pyoverdines are non-ribosomally synthesized, highly modified peptides whose biosynthesis and regulation involve more than 20 proteins (4). The cytoplasmic biosynthesis reactions are well established, but recently, the periplasmic maturation has gained interest. Of the five periplasmic enzymes, PvdM, PvdN, PvdO, PvdP, and PvdQ, which are found in all known pyoverdine-producing species, functions have been assigned so far only to PvdQ and PvdP, which are involved in a precursor deacylation step and the chromophore cyclization, respectively (5-8). PvdQ has been identified as a potential novel drug target (5). Based on interposon mutagenesis studies, PvdM, PvdN, and PvdO are all considered to be essential for the formation of functional pyoverdines (6, 9 -11).PvdN is translocated via the Tat 2 system (11). As heterologously produced PvdN contains as prosthetic group a pyridoxal phosphate cofactor (PLP (12)), the Tat system may transport PvdN together with a bound PLP or a derivative...

show abstract

Section: Functional Role Of Pvdnmentioning

confidence: 99%

“…In related PLP-containing enzymes, a lysine residue is conserved that plays a crucial role in cofactor binding (25). The corresponding residue in PvdN from P. fluorescens A506 is Lys-261.…”

Section: The Modified Pyoverdine Is Not Required For Iron-limited Gromentioning

confidence: 99%

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

Ringel

Dräger

Brüser

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…These enzymes carry out a variety of reactions, such as transamination, racemization, deamination, decarboxylation, elimination, and replacement, using PLP as an electron sink for stabilization of reaction intermediates. They have been classified into four major folds (I-IV) based on their structure and sequence similarities (10,11). Diaminopropionate ammonialyase (DAPAL) (EC 4.3.1.15), a prokaryotic enzyme, has been classified as a fold type II PLP-dependent enzyme, although it shares low sequence identity (18 -23%) with other well studied fold type II enzymes.…”

mentioning

confidence: 99%

Crystal Structure of Escherichia coli Diaminopropionate Ammonia-lyase Reveals Mechanism of Enzyme Activation and Catalysis

Bisht

Radha

Bharath

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: DAPAL is a novel PLP-dependent enzyme involved in the degradation of DAP, a nonstandard amino acid. Results: Striking structural differences were observed between apo-and holo-EcDAPAL, and structure with a PLP-aminoacrylate intermediate bound at the active site was obtained. Conclusion: Enzyme undergoes apo to holo structural transitions and follows a two-base mechanism of catalysis. Significance: The results provide insights into the catalytic mechanism of DAPAL.

show abstract

“…However, vitamin B6 supplements must be administered with caution. Whereas PLP activates the synthesis of GABA from glutamate (Jansonius et al, 1998), it also activates GABA transaminase, the enzyme that degrades GABA (Mueller et al, 2001), and an increase in cerebral GABA is the base of action of valproic acid.…”

Section: Discussionmentioning

confidence: 99%

Plasma vitamin values and antiepileptic therapy: Case reports of pregnancy outcomes affected by a neural tube defect

Candito

Naïmi

Boisson

et al. 2006

Birth Defects Research

View full text Add to dashboard Cite

BACKGROUND: Folic acid supplementation reduces the occurrence of neural tube defects (NTDs); however, it is not clear whether it protects against teratogenic effects of antiepileptic drugs. METHODS: We report the cases of four pregnant women receiving valproic acid therapy, who all had NTD-affected offspring, despite periconceptional 5 mg/day of folic acid supplementation (cases), and investigated homocysteine metabolism, linked with folate metabolism. Their plasma homocysteine, folates, and vitamin B6 and B12 results were compared with values of two other women, who were also receiving valproic acid and folic acid complement, but who had normal pregnancies (valproic acid controls), and values of 40 pregnant women who had normal pregnancies and were not receiving any therapy (controls without therapy). Because of the possible existence of a genetic susceptibility, polymorphisms in homocysteine metabolism were sought. RESULTS: Two cases showed a decreased phosphopyridoxal level, compared with levels in the controls not receiving therapy. The genotype TT (C677T) is an NTD genetic susceptibility, but it was observed in only one valproic acid control. Various polymorphisms were observed in the cases, but were also common in the controls. Several studies have reported that valproic acid therapy lowers vitamin B6 levels. Our case with the greatest decrease in plasma phosphopyridoxal, who was taking periconceptional folic acid plus pyridoxine therapy, had a normal second pregnancy outcome. CONCLUSIONS: In addition to folates, other vitamins, such as vitamin B6, may have played a role in NTDs in our patients taking an antiepileptic drug. Birth Defects Research (Part A) 79: 62-64, 2007.

show abstract

Structure, evolution and action of vitamin B6-dependent enzymes

Cited by 393 publications

References 53 publications

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

Crystal Structure of Escherichia coli Diaminopropionate Ammonia-lyase Reveals Mechanism of Enzyme Activation and Catalysis

Plasma vitamin values and antiepileptic therapy: Case reports of pregnancy outcomes affected by a neural tube defect

Contact Info

Product

Resources

About