A heme degradation enzyme, HutZ, from Vibrio cholerae

Uchida, Takeshi; Sekine, Yukari; Matsui, Toshitaka; Ikeda‐Saito, Masao; Ishimori, Koichiro

doi:10.1039/c2cc31147j

Cited by 35 publications

(152 citation statements)

References 24 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…HoloHupZ in SPB containing CPR, NADPH regeneration system, and catalase (as described above) was allowed to react for 5 h. The reaction mixture was then acidified with 10 mM HCl, and partitioned into pyridine (33 %) as described by (Uchida et al 2012). …”

Section: Acidification and Pyridine Extractionmentioning

confidence: 99%

“…A new family of bacterial proteins that degrade heme in vitro and have no homology to previously described enzymes was recently uncovered in Campylobacter jejuni (ChuZ) (Zhang et al 2011), Helicobacter pylori (HugZ) (Guo et al 2008;Hu et al 2011) and Vibrio cholerae (HutZ) (Liu et al 2012b;Uchida et al 2012). Proteins from this family form homodimers with a split b-barrel fold that is characteristic of FMN-binding proteins, but no FMN binding was demonstrated.…”

Section: Introductionmentioning

confidence: 95%

“…Like PigA, HugZ exhibits d-meso regiospecificity for cleaving the ring in the heme molecule (Guo et al 2008). Although the exact nature of the bilin produced by HutZ or ChuZ reactions were not defined yet, HutZ is suggested to have b-or d-meso regioselectivity (Uchida et al 2012).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus

et al. 2016

View full text Add to dashboard Cite

In Group A streptococcus (GAS), the metallorepressor MtsR regulates iron homeostasis. Here we describe a new MtsR-repressed gene, which we named hupZ (heme utilization protein). A recombinant HupZ protein was purified bound to heme from Escherichia coli grown in the presence of 5-aminolevulinic acid and iron. HupZ specifically binds heme with stoichiometry of 1:1. The addition of NADPH to heme-bound HupZ (in the presence of cytochrome P450 reductase, NADPH-regeneration system and catalase) triggered progressive decrease of the HupZ Soret band and the appearance of an absorption peak at 660 nm that was resistance to hydrolytic conditions. No spectral changes were observed when ferredoxin and ferredoxin reductase were used as redox partners. Differential spectroscopy with myoglobin or with the ferrous chelator, ferrozine, confirmed that carbon monoxide and free iron are produced during the reaction. ApoHupZ was crystallized as a homodimer with a split β-barrel conformation in each monomer comprising six β strands and three α helices. This structure resembles the split β-barrel domain shared by the members of a recently described family of heme degrading enzymes. However, HupZ is smaller and lacks key residues found in the proteins of the latter group. Phylogenetic analysis places HupZ on a clade separated from those for previously described heme oxygenases. In summary, we have identified a new GAS enzyme-containing split β-barrel and capable of heme biotransformation in vitro; to the best of our knowledge, this is the first enzyme among Streptococcus species with such activity.

show abstract

Section: Acidification and Pyridine Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A candidate for a heme oxygenase-like enzyme to degrade heme is the cytoplasmic protein HutZ, which is needed for the efficient use of heme as an iron source in V. cholerae (122). An analysis of HutZ in vitro indicated that it has a high affinity for heme and degrades it via the same intermediates as heme oxygenase (123). Thus, HutZ may serve to release iron from heme following transport.…”

Section: Transport Of Iron Complexesmentioning

confidence: 99%

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Payne

Mey

Wyckoff

2016

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYIron is an essential element forVibriospp., but the acquisition of iron is complicated by its tendency to form insoluble ferric complexes in nature and its association with high-affinity iron-binding proteins in the host. Vibrios occupy a variety of different niches, and each of these niches presents particular challenges for acquiring sufficient iron.Vibriospecies have evolved a wide array of iron transport systems that allow the bacteria to compete for this essential element in each of its habitats. These systems include the secretion and uptake of high-affinity iron-binding compounds (siderophores) as well as transport systems for iron bound to host complexes. Transporters for ferric and ferrous iron not complexed to siderophores are also common toVibriospecies. Some of the genes encoding these systems show evidence of horizontal transmission, and the ability to acquire and incorporate additional iron transport systems may have allowedVibriospecies to more rapidly adapt to new environmental niches. While too little iron prevents growth of the bacteria, too much can be lethal. The appropriate balance is maintained in vibrios through complex regulatory networks involving transcriptional repressors and activators and small RNAs (sRNAs) that act posttranscriptionally. Examination of the number and variety of iron transport systems found inVibriospp. offers insights into how this group of bacteria has adapted to such a wide range of habitats.

show abstract

“…Furthermore, the biological degradation of heme (iron-protoporphyrin) plays a variety of critical functions in living organisms [39]; an enzyme termed heme oxygenase (HO) has already been reported to catalyze the regiospecific conversion of heme into biliverdin, carbon monoxide (CO), and a free ferrous iron via three successive oxygenation reactions [40] (Scheme 4). The literature contains numerous reports exemplifying other types of heme degradation enzymes, e.g., the HutZ protein in the heme utilization (Hut) system [41,42] and Mycobacterium tuberculosis enzyme MhuD [43]. Therefore, the results in the present work newly indicate that (1) oxygen will bind at the distal site for oxygen activation to be oxoferric (Fe III −O-O − ) species; (2) the iron of porphyrin/Fe and oxygen coordinates solely in water due to the promotion of oxoferryl (Fe IV =O) species; (3) ESR low-spin signals (g = 2.8, 2.22, and 1.72) disappear for oxygen activation with high-spin signal contamination; and (4) HasA can be used for cyclic deracemization in combination with NaBH4.…”

Section: * Reactionsmentioning

confidence: 99%

Heterogeneous Asymmetric Oxidation Catalysis Using Hemophore HasApf. Application in the Chemoenzymatic Deracemization of sec-Alcohols with Sodium Borohydride

Nagaoka

2016

Catalysts

View full text Add to dashboard Cite

Abstract:This study aims to demonstrate the coordination of oxygen regarding the hemophore HasApf expressed by Escherichia coli cells, which appears to create an unlikely oxygen-activating system in HasA due to the already-coordinated iron.In the asymmetric oxidation of rac-1-(6-methoxynaphthalen-2-yl)ethanol (rac-1) using dissolved oxygen, the signals at g-values of 2.8, 2.22, and 1.72 in the electron spin resonance (ESR) spectra disappeared in conjunction with the promotion of oxoferric (Fe III´O -O´) species in the distal site. These results suggest that the iron of porphyrin/Fe may be oxidized in water, leading to exhibition of greater asymmetric oxidation activity in the promotion of oxoferryl (Fe IV =O) species. A ketone (~50% chemical yield) produced from (R)-(´)-sec-alcohol can be desymmetrized by NaBH 4 in aqueous medium at 40˝C (>99% enantiomer excess, ee, >90% chemical yield) in the absence of NAD(P). Therefore, HasA can be regenerated via successive asymmetric catalytic events through an incorporated iron electron-transfer system in the presence of oxygen: Fe II + O 2 Ñ Fe III´O -O´Ñ Fe IV =O (oxidizing rac-1) Ñ Fe II + H 2 O. This process is similar to a Fenton reaction. The use of a HasA-catalytic system with an incorporated redox cofactor for asymmetric oxidation overcomes the apparent difficulties in working with pure dehydrogenase enzyme/redox cofactor systems for biotransformations.

show abstract

A heme degradation enzyme, HutZ, from Vibrio cholerae

Cited by 35 publications

References 24 publications

In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus

In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Heterogeneous Asymmetric Oxidation Catalysis Using Hemophore HasApf. Application in the Chemoenzymatic Deracemization of sec-Alcohols with Sodium Borohydride

Contact Info

Product

Resources

About