Heme oxygenase: Difference between revisions
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<StructureSection load='2dy5' size='350' side='right' caption='Rat heme oxygenase complex with imidazole derivative and Cl- ion (green) (PDB entry [[2dy5]])' scene=''> | |||
__TOC__ | __TOC__ | ||
==='''General Information'''=== | ==='''General Information'''=== | ||
---- | ---- | ||
Heme Oxygenase (HO) is a member of the Hemoprotein family and catalyzes the Oxygen-dependent cleavage of the porphyrin ring of heme, using reducing equivalents like NADH to produce biliverdin, iron and CO <ref name="HO">PMID:17253780</ref>. HO consists of two main isoforms which are present in mammals, HO-1 and HO-2. The two isoforms are products of different genes, are different molecular sizes (32 kDa and 36 kDa respectively) and contain a different primary structure showing only 58% homology <ref name="HO1">PMID:15522396</ref>. However studies have shown that the two isoforms share a region with 100% secondary structure homology which is believed to be the catalytic site of the protein<ref name="HO"/>. The heme oxygenase isoforms are not free throughout the body but sequestered to certain tissues. | '''Heme Oxygenase''' (HO) is a member of the [[Hemeproteins|Hemoprotein family]] and catalyzes the Oxygen-dependent cleavage of the porphyrin ring of heme, using reducing equivalents like NADH to produce biliverdin, iron and CO <ref name="HO">PMID:17253780</ref>. HO consists of two main isoforms which are present in mammals, HO-1 and HO-2. The two isoforms are products of different genes, are different molecular sizes (32 kDa and 36 kDa respectively) and contain a different primary structure showing only 58% homology <ref name="HO1">PMID:15522396</ref>. However studies have shown that the two isoforms share a region with 100% secondary structure homology which is believed to be the catalytic site of the protein<ref name="HO"/>. The heme oxygenase isoforms are not free throughout the body but sequestered to certain tissues. | ||
*'''Heme oxygenase -1''' is inducible and is strongly expressed in the spleen and liver. | |||
*'''Heme Oxygenase-2''' is expressed constitutively and is strongly expressed in the brain, testis and vascular systems<ref name="sc1">PMID:12909459</ref>. | |||
==='''Ligand'''=== | ==='''Ligand'''=== | ||
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==='''Structure'''=== | ==='''Structure'''=== | ||
---- | ---- | ||
HO is a 233 residue protein with a secondary structure consisting of <scene name='Sandbox_Reserved_308/7_helces/1'> seven α-helices </scene> which interacts with a <scene name='Sandbox_Reserved_308/Heme_group/1'> heme group </scene> <ref name="HO"/> at the optimum pH of 7.4; at 37 degrees C <ref name="PH">PMID:2158889</ref>. The heme is sandwiched between two helices termed the <scene name='Sandbox_Reserved_308/Prox_dis/1'> proximal and distal helices </scene> <ref name="HO3">PMID:18798608</ref>. The proximal helix provides the His 25 heme ligand along with the various contact residues (Ala 28 and Glu 29), but also Thr 21 which contacts the heme through a water molecule <ref name="HO"/>. On the distal side where the ligands binds (the catalytic site) there is a highly conserved sequence of Glycine residues (<scene name='Sandbox_Reserved_308/Test/4'>Gly 139, Gly 143-144</scene>) that provide a required flexibility for the reaction to occur <ref name="HO"/>. This results in the backbone atoms of Gly 139 and Gly 143 to directly contact the heme. Inhibition of HO is provided by compounds such as imidazole-dioxolane which disrupt this flexibility, thereby forcing the HO protein to become rigid, stopping its function <ref name="sc2">PMID:3290025</ref>. | HO is a 233 residue protein with a secondary structure consisting of <scene name='Sandbox_Reserved_308/7_helces/1'> seven α-helices </scene> which interacts with a <scene name='Sandbox_Reserved_308/Heme_group/1'> heme group </scene> <ref name="HO"/> at the optimum pH of 7.4; at 37 degrees C <ref name="PH">PMID:2158889</ref>. The heme is sandwiched between two helices termed the <scene name='Sandbox_Reserved_308/Prox_dis/1'> proximal and distal helices </scene> <ref name="HO3">PMID:18798608</ref>. The proximal helix provides the His 25 heme ligand along with the various contact residues (Ala 28 and Glu 29), but also Thr 21 which contacts the heme through a water molecule <ref name="HO"/>. On the distal side where the ligands binds (the catalytic site) there is a highly conserved sequence of Glycine residues (<scene name='Sandbox_Reserved_308/Test/4'>Gly 139, Gly 143-144</scene>) that provide a required flexibility for the reaction to occur <ref name="HO"/>. This results in the backbone atoms of Gly 139 and Gly 143 to directly contact the heme. Inhibition of HO is provided by compounds such as imidazole-dioxolane which disrupt this flexibility, thereby forcing the HO protein to become rigid, stopping its function <ref name="sc2">PMID:3290025</ref>. | ||
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==Additional Resources== | ==Additional Resources== | ||
For additional information, | For additional information, see: | ||
*[[Cancer]] | |||
*[[NADPH Cytochrome P450 Oxidoreductase]] | |||
*[[Hemeproteins]] | |||
==3D structures of heme oxygenase== | |||
[[Heme oxygenase 3D structures]] | |||
</StructureSection> | |||
==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | |||
This page originally authored by Barinder Chahal | This page originally authored by Barinder Chahal | ||