An Unconventional Hexacoordinated Flavohemoglobin from Mycobacterium tuberculosis

Gupta, Sanjay; Pawaria, Sudesh; Lu, Chong‐Dao; Hade, Mangesh Dattu; Singh, Chaahat; Yeh, Syun Ru; Dikshit, Kanak L.

doi:10.1074/jbc.m111.329920

Cited by 17 publications

(27 citation statements)

References 54 publications

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“…The Soret for the globin heme (the C539A variant) is observed at 413 nm ( Fig. 3C), similar to a flavohemoglobin from M. tuberculosis (414 nm) (31,32), and the NOS ox heme Soret at 417 nm (Fig. 3B) is more similar that of the NOS protein from S. cellulosum (416 nm) (27).…”

Section: Spectroscopic Propertiesmentioning

confidence: 62%

A nitric oxide synthase–like protein from Synechococcus produces NO/NO3− from l-arginine and NAPDH in a tetrahydrobiopterin- and Ca2+-dependent manner

Picciano

Crane

2019

Journal of Biological Chemistry

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Section: Spectroscopic Propertiesmentioning

confidence: 62%

A nitric oxide synthase–like protein from Synechococcus produces NO/NO3− from l-arginine and NAPDH in a tetrahydrobiopterin- and Ca2+-dependent manner

Picciano

Crane

2019

Journal of Biological Chemistry

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“…Heme content of the protein or cells was determined by using pyridine ferrohemochromogen method as described earlier . The association of FAD with FHb1 was checked using published procedure . Briefly, flavin cofactor was extracted after boiling the sample for 5 min and centrifuged at 14,000 rpm for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…M. smegmatis is an opportunistic pathogen and fast‐growing species of mycobacteria that carries both type I and type II classes of flavoHbs, indicating that they may be playing different functions in the cellular metabolism of their host. Type II flavoHb of M. smegmatis displays close similarity with a flavoHb (MtbFHb) of M. tuberculosis and may have similar cellular functions. Structure‐based sequence alignment of type I flavohemoglobin (FHb1) of M. smegmatis indicated that it may be related to classical flavoHbs that are involved in diverse redox reactions including NO scavenging and detoxification.…”

Section: Introductionmentioning

confidence: 99%

Type I flavohemoglobin of mycobacterium smegmatis is a functional nitric oxide dioxygenase

et al. 2014

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Two flavohemoglobins, type I and type II, displaying distinct structural features and cofactor binding sites coexist in Mycobacterium smegmatis; however, none of these flavohemeproteins are characterized so far. We have cloned and expressed type I flavohemoglobin (FHb1) of Mycobacterium smegmatis, encoded by MSMEG_1336, and characterized its spectral and functional properties. FHb1 exists as a monomer and displays spectral and functional characteristics similar to HMP of E. coli. Specific NO dioxygenase (NOD) activity of FHb1 was estimated to be 63.5 nmol heme 21 sec 21 , which was nearly eightfold higher than the HbN of M. tuberculosis and matched closely to the HMP of E. coli on the basis of cellular heme content. FHb1 preferred NADH for the NO dioxygenation and exhibited rapid reduction of flavin adenine dinucleotide and heme iron using NADH as electron donor. Level of FHb1 transcript increased significantly in M. smegmatis in the presence of acidified nitrite, and a nitric oxide-responsive transcriptional regulator of Rrf2 family exists together with the FHb1 under the same operon. These results suggested that FHb1 of M. smegmatis is a functional NOD and may be involved in the stress management of its host toward nitric oxide and nitrosative stress.

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“…Aspergillus oryzae , A. nidulans, and A. fumigatus express 2 flavoHbs showing a NOD function [112–114]. Erwinia chrysanthemi [115], Giardia intestinalis [116], G. lamblia [117], and Mycobacterium tuberculosis [118, 119] flavoHbs have been also investigated. The E. chrysanthemi and Giardia flavoHbs show appreciable NOD activity in vitro

\begin{matrix} 2 NO + 2 O_{2} + NAD (P) H \\ \to {2 {NO}_{3}}^{-} + NAD {(P)}^{+} + H^{+} \end{matrix}

…”

Section: Flavohbs Hbs and Mbs Function As No-metabolizing Enzymesmentioning

confidence: 99%

“…The protein is hexa-coordinate and shows very low NOD activity [119] and little ability to protect against nitrosative stress imposed by acidified nitrite when expressed in E. coli or M. smegmatis [118]. A function as a D-lactate specific dehydrogenase was suggested.…”

Section: Other Enzymatic Functions For Hemoglobins?mentioning

confidence: 99%

Hemoglobin: A Nitric-Oxide Dioxygenase

Gardner

2012

Scientifica

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Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry.

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An Unconventional Hexacoordinated Flavohemoglobin from Mycobacterium tuberculosis

Cited by 17 publications

References 54 publications

A nitric oxide synthase–like protein from Synechococcus produces NO/NO3− from l-arginine and NAPDH in a tetrahydrobiopterin- and Ca2+-dependent manner

A nitric oxide synthase–like protein from Synechococcus produces NO/NO3− from l-arginine and NAPDH in a tetrahydrobiopterin- and Ca2+-dependent manner

Type I flavohemoglobin of mycobacterium smegmatis is a functional nitric oxide dioxygenase

Hemoglobin: A Nitric-Oxide Dioxygenase

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