1ubb: Difference between revisions

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Crystal structure of rat HO-1 in complex with ferrous heme

OverviewOverview

Heme oxygenase (HO) catalyzes heme degradation by utilizing O(2) and reducing equivalents to produce biliverdin IX alpha, iron, and CO. To avoid product inhibition, the heme[bond]HO complex (heme[bond]HO) is structured to markedly increase its affinity for O(2) while suppressing its affinity for CO. We determined the crystal structures of rat ferrous heme[bond]HO and heme[bond]HO bound to CO, CN(-), and NO at 2.3, 1.8, 2.0, and 1.7 A resolution, respectively. The heme pocket of ferrous heme-HO has the same conformation as that of the previously determined ferric form, but no ligand is visible on the distal side of the ferrous heme. Fe[bond]CO and Fe[bond]CN(-) are tilted, whereas the Fe[bond]NO is bent. The structure of heme[bond]HO bound to NO is identical to that bound to N(3)(-), which is also bent as in the case of O(2). Notably, in the CO- and CN(-)-bound forms, the heme and its ligands shift toward the alpha-meso carbon, and the distal F-helix shifts in the opposite direction. These shifts allow CO or CN(-) to bind in a tilted fashion without a collision between the distal ligand and Gly139 O and cause disruption of one salt bridge between the heme and basic residue. The structural identity of the ferrous and ferric states of heme[bond]HO indicates that these shifts are not produced on reduction of heme iron. Neither such conformational changes nor a heme shift occurs on NO or N(3)(-) binding. Heme[bond]HO therefore recognizes CO and O(2) by their binding geometries. The marked reduction in the ratio of affinities of CO to O(2) for heme[bond]HO achieved by an increase in O(2) affinity [Migita, C. T., Matera, K. M., Ikeda-Saito, M., Olson, J. S., Fujii, H., Yoshimura, T., Zhou, H., and Yoshida, T. (1998) J. Biol. Chem. 273, 945-949] is explained by hydrogen bonding and polar interactions that are favorable for O(2) binding, as well as by characteristic structural changes in the CO-bound form.

About this StructureAbout this Structure

1UBB is a Single protein structure of sequence from Rattus norvegicus with as ligand. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of ferrous and CO-, CN(-)-, and NO-bound forms of rat heme oxygenase-1 (HO-1) in complex with heme: structural implications for discrimination between CO and O2 in HO-1., Sugishima M, Sakamoto H, Noguchi M, Fukuyama K, Biochemistry. 2003 Aug 26;42(33):9898-905. PMID:12924938

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-[[Image:1ubb.jpg|left|200px]]<br /><applet load="1ubb" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ubb.jpg|left|200px]]<br /><applet load="1ubb" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ubb, resolution 2.30&Aring;" />
 '''Crystal structure of rat HO-1 in complex with ferrous heme'''<br />
 ==Overview==
-Heme oxygenase (HO) catalyzes heme degradation by utilizing O(2) and, reducing equivalents to produce biliverdin IX alpha, iron, and CO. To, avoid product inhibition, the heme[bond]HO complex (heme[bond]HO) is, structured to markedly increase its affinity for O(2) while suppressing, its affinity for CO. We determined the crystal structures of rat ferrous, heme[bond]HO and heme[bond]HO bound to CO, CN(-), and NO at 2.3, 1.8, 2.0, and 1.7 A resolution, respectively. The heme pocket of ferrous heme-HO has, the same conformation as that of the previously determined ferric form, but no ligand is visible on the distal side of the ferrous heme., Fe[bond]CO and Fe[bond]CN(-) are tilted, whereas the Fe[bond]NO is bent., The structure of heme[bond]HO bound to NO is identical to that bound to, N(3)(-), which is also bent as in the case of O(2). Notably, in the CO-, and CN(-)-bound forms, the heme and its ligands shift toward the, alpha-meso carbon, and the distal F-helix shifts in the opposite, direction. These shifts allow CO or CN(-) to bind in a tilted fashion, without a collision between the distal ligand and Gly139 O and cause, disruption of one salt bridge between the heme and basic residue. The, structural identity of the ferrous and ferric states of heme[bond]HO, indicates that these shifts are not produced on reduction of heme iron., Neither such conformational changes nor a heme shift occurs on NO or, N(3)(-) binding. Heme[bond]HO therefore recognizes CO and O(2) by their, binding geometries. The marked reduction in the ratio of affinities of CO, to O(2) for heme[bond]HO achieved by an increase in O(2) affinity [Migita, C. T., Matera, K. M., Ikeda-Saito, M., Olson, J. S., Fujii, H., Yoshimura, T., Zhou, H., and Yoshida, T. (1998) J. Biol. Chem. 273, 945-949] is, explained by hydrogen bonding and polar interactions that are favorable, for O(2) binding, as well as by characteristic structural changes in the, CO-bound form.
+Heme oxygenase (HO) catalyzes heme degradation by utilizing O(2) and reducing equivalents to produce biliverdin IX alpha, iron, and CO. To avoid product inhibition, the heme[bond]HO complex (heme[bond]HO) is structured to markedly increase its affinity for O(2) while suppressing its affinity for CO. We determined the crystal structures of rat ferrous heme[bond]HO and heme[bond]HO bound to CO, CN(-), and NO at 2.3, 1.8, 2.0, and 1.7 A resolution, respectively. The heme pocket of ferrous heme-HO has the same conformation as that of the previously determined ferric form, but no ligand is visible on the distal side of the ferrous heme. Fe[bond]CO and Fe[bond]CN(-) are tilted, whereas the Fe[bond]NO is bent. The structure of heme[bond]HO bound to NO is identical to that bound to N(3)(-), which is also bent as in the case of O(2). Notably, in the CO- and CN(-)-bound forms, the heme and its ligands shift toward the alpha-meso carbon, and the distal F-helix shifts in the opposite direction. These shifts allow CO or CN(-) to bind in a tilted fashion without a collision between the distal ligand and Gly139 O and cause disruption of one salt bridge between the heme and basic residue. The structural identity of the ferrous and ferric states of heme[bond]HO indicates that these shifts are not produced on reduction of heme iron. Neither such conformational changes nor a heme shift occurs on NO or N(3)(-) binding. Heme[bond]HO therefore recognizes CO and O(2) by their binding geometries. The marked reduction in the ratio of affinities of CO to O(2) for heme[bond]HO achieved by an increase in O(2) affinity [Migita, C. T., Matera, K. M., Ikeda-Saito, M., Olson, J. S., Fujii, H., Yoshimura, T., Zhou, H., and Yoshida, T. (1998) J. Biol. Chem. 273, 945-949] is explained by hydrogen bonding and polar interactions that are favorable for O(2) binding, as well as by characteristic structural changes in the CO-bound form.
 ==About this Structure==
-UBB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with HEM as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UBB OCA].
+UBB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=HEM:'>HEM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UBB OCA].
 ==Reference==
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 [[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:58:38 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:37 2008''