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Information on EC 1.14.99.57 - heme oxygenase (mycobilin-producing) and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WKH3

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IUBMB Comments
The enzyme, characterized from the bacterium Mycobacterium tuberculosis, is involved in heme degradation and iron utilization. The enzyme binds two stacked protoheme molecules per monomer. Unlike the canonical heme oxygenases, the enzyme does not release carbon monoxide or formaldehyde. Instead, it forms unique products, named mycobilins, that retain the alpha-meso-carbon at the ring cleavage site as an aldehyde group. EC 1.6.2.4, NADPH-hemoprotein reductase, can act as electron donor in vitro.
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Mycobacterium tuberculosis
UNIPROT: P9WKH3
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The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The enzyme appears in selected viruses and cellular organisms
Synonyms
rv3592, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heme-degrading monooxygenase HmoB
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mycobacterial heme utilization, degrader
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mhuD
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
protoheme,donor:oxygen oxidoreductase (mycobilin-producing)
The enzyme, characterized from the bacterium Mycobacterium tuberculosis, is involved in heme degradation and iron utilization. The enzyme binds two stacked protoheme molecules per monomer. Unlike the canonical heme oxygenases, the enzyme does not release carbon monoxide or formaldehyde. Instead, it forms unique products, named mycobilins, that retain the alpha-meso-carbon at the ring cleavage site as an aldehyde group. EC 1.6.2.4, NADPH-hemoprotein reductase, can act as electron donor in vitro.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
protoheme + 3 reduced acceptor + 3 O2
mycobilin a + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
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?
protoheme + 3 reduced acceptor + 3 O2
mycobilin b + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
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-
-
?
additional information
?
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MhuD catalysis does not generate CO. MhuD cleaves heme at the alpha-meso position but retains the meso-carbon atom at the cleavage site. The tetrapyrrole product of MhuD, mycobilin, has an aldehyde group at the cleavage site and a carbonyl group at either the beta-meso or the delta-meso position. MhuD catalysis does not involve verdoheme
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
protoheme + 3 reduced acceptor + 3 O2
mycobilin a + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
-
-
-
?
protoheme + 3 reduced acceptor + 3 O2
mycobilin b + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
-
-
-
?
additional information
?
-
MhuD catalysis does not generate CO. MhuD cleaves heme at the alpha-meso position but retains the meso-carbon atom at the cleavage site. The tetrapyrrole product of MhuD, mycobilin, has an aldehyde group at the cleavage site and a carbonyl group at either the beta-meso or the delta-meso position. MhuD catalysis does not involve verdoheme
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-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
cyanide-inhibited MhuD in complex with heme as well as detailed characterization of this species. There is no evidence for an ordered network of water molecules on the distal side of the heme substrate. The degree of heme ruffling in the crystal structure is greater than that observed for heme oxygenases and less than that observed for heme-degrading enzyme IsdI. The Fe 3dxz-, 3dyz-, and 3dxy-based molecular orbitals are very close in energy, and the room-temperature 1H NMR spectrum is consistent with population of both a 2Eg electronic state with a (dxy)2(dxz,dyz)3 electron configuration, and a 2B2g state with a (dxz,dyz)4(dxy)1 electron configuration. MhuD-heme-CN has a 2B2g electronic ground state with a low-lying 2Eg excited state
MhuD-diheme complex, to 1.75 A resolution, reveals two stacked hemes forming extensive contacts with residues in the active site. The solvent-exposed heme is axially liganded by His75 and is stacked planar upon the solvent-protected heme. The solvent-protected heme is coordinated by a chloride ion which is, in turn, stabilized by residue Asn7
the catalytically active 1:1 heme-MhuD complex has an active site structure similar to those of heme degrading enzymes IsdG and IsdI, including the nonplanarity (ruffling) of the heme group bound to the enzyme
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
W66A
steric bulk at residue 66 promotes MhuD-catalyzed heme oxygenation, and this reaction does not depend upon the generation of free peroxide. The protein fold is similar to wild-type
W66F
steric bulk at residue 66 promotes MhuD-catalyzed heme oxygenation, and this reaction does not depend upon the generation of free peroxide. The protein fold is similar to wild-type
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Graves, A.B.; Morse, R.P.; Chao, A.; Iniguez, A.; Goulding, C.W.; Liptak, M.D.
Crystallographic and spectroscopic insights into heme degradation by Mycobacterium tuberculosis MhuD
Inorg. Chem.
53
5931-5940
2014
Mycobacterium tuberculosis (P9WKH3), Mycobacterium tuberculosis ATCC 25618 (P9WKH3)
Manually annotated by BRENDA team
Nambu, S.; Matsui, T.; Goulding, C.W.; Takahashi, S.; Ikeda-Saito, M.
A new way to degrade heme: the Mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO
J. Biol. Chem.
288
10101-10109
2013
Mycobacterium tuberculosis (P9WKH3), Mycobacterium tuberculosis H37Rv (P9WKH3)
Manually annotated by BRENDA team
Chim, N.; Iniguez, A.; Nguyen, T.Q.; Goulding, C.W.
Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis
J. Mol. Biol.
395
595-608
2010
Mycobacterium tuberculosis (P9WKH3), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WKH3)
Manually annotated by BRENDA team
Graves, A.B.; Graves, M.T.; Liptak, M.D.
Measurement of heme ruffling changes in MhuD using UV-vis pectroscopy
J. Phys. Chem. B
120
3844-3853
2016
Mycobacterium tuberculosis (P9WKH3), Mycobacterium tuberculosis ATCC 25618 (P9WKH3)
Manually annotated by BRENDA team