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Catalytic Site Atlas

CSA LITERATURE entry for 1wnw

E.C. nameheme oxygenase
SpeciesCorynebacterium diphtheriae ()
E.C. Number (IntEnz) 1.14.99.3
CSA Homologues of 1wnwThere are 53 Homologs
CSA Entries With UniProtID P71119
CSA Entries With EC Number 1.14.99.3
PDBe Entry 1wnw
PDBSum Entry 1wnw
MACiE Entry 1wnw

Literature Report

IntroductionHeme oxygenase (HO) catalyses the breakdown of heme to release biliverdin, CO, and free iron, and is found in mammals, plants and photosynthetic bacteria. The roles of the heme catabolism process are different in mammals and plants: whilst mammals use HO to degrade excess heme from red blood cells, plants and cyanobacteria use HO activity in order to generate the biliverdin needed for the production of light harvesting complexes. As a result, their is little sequence or structural homology between the mammalian and other forms, indicating that they may have evolved independently. However, the reaction seems to proceed via the same mechanism in both, with key active site residues being the same between the two groups. The bacterial form is described here, but the catalytic residues are the same in both the mammalian and plant forms of the enzyme.
MechansimThe reaction proceeds via a series of reaction intermediates involving the heme iron in different oxidation states. In the first stage of the reaction, dioxygen binds to the iron (III) ion in heme, and accepts an electron from the surrounding environment causing heterolytic fission of the pi bond. Concomitant protonation of the dioxygen by a water molecule, activated by Asp 136, results in the formation of an Fe-OOH species. The OH group then acts as a nucleophile, attacking the alpha position of the porphyrin ring. Steric strain from Gly 135 and Gly 140 causes the destabilisation of all the other possible positions, thus stabilising the alpha meso hydroxylated intermediate. Binding of oxygen to this species liberates CO and forms Fe2+, which is then released when another molecule of dioxygen binds to the heme and cleaves the central cycle to form the biliverdin product. Thus the heme substrate acts as a cofactor in the reaction, by activating the dioxygen.
Reaction

Catalytic Sites for 1wnw

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnA136136macie:sideChainActs to activate a water molecule through electrostatic contacts, thus allowing the water molecule to act as an acid base for the reaction.
GlyA140140macie:sideChainThrough steric strain, destabilises hydroxy form of heme at every position except for alpa, thus stabilises this form relative to the others.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnB136136macie:sideChainActs to activate a water molecule through electrostatic contacts, thus allowing the water molecule to act as an acid base for the reaction.
GlyB140140macie:sideChainThrough steric strain, destabilises hydroxy form of heme at every position except for alpa, thus stabilises this form relative to the others.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnC136136macie:sideChainActs to activate a water molecule through electrostatic contacts, thus allowing the water molecule to act as an acid base for the reaction.
GlyC140140macie:sideChainThrough steric strain, destabilises hydroxy form of heme at every position except for alpa, thus stabilises this form relative to the others.

Literature References

Notes:
Matsui T
Roles of distal Asp in heme oxygenase from Corynebacterium diphtheriae, HmuO: A water-driven oxygen activation mechanism.
J Biol Chem 2005 280 2981-2989
PubMed: 15528205
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