1twr
|
Crystal structures of ferrous and ferrous-NO forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage
OverviewOverview
Heme oxygenase oxidatively degrades heme to biliverdin resulting in the, release of iron and CO through a process in which the heme participates, both as a cofactor and substrate. One of the least understood steps in the, heme degradation pathway is the conversion of verdoheme to biliverdin. In, order to obtain a better understanding of this step we report the crystal, structures of ferrous-verdoheme and, as a mimic for the oxy-verdoheme, complex, ferrous-NO verdoheme in a complex with human HO-1 at 2.20 and, 2.10 A, respectively. In both structures the verdoheme occupies the same, binding location as heme in heme-HO-1, but rather than being ruffled, verdoheme in both sets of structures is flat. Both structures are similar, to their heme counterparts except for the distal helix and heme pocket, solvent structure. In the ferrous-verdoheme structure the distal helix, moves closer to the verdoheme, thus tightening the active site. NO binds, to verdoheme in a similar bent conformation to that found in heme-HO-1., The bend angle in the verodoheme-NO structure places the terminal NO, oxygen 1 A closer to the alpha-meso oxygen of verdoheme compared to the, alpha-meso carbon on the heme-NO structure. A network of water molecules, which provide the required protons to activate the iron-oxy complex of, heme-HO-1, is absent in both ferrous-verdoheme and the verdoheme-NO, structure.
DiseaseDisease
Known diseases associated with this structure: Epiphyseal dysplasia, multiple, 5 OMIM:[602109], Heme oxygenase-1 deficiency OMIM:[141250], Osteoarthritis, hand, susceptibility to OMIM:[602109], Spondyloepimetaphyseal dysplasia OMIM:[602109]
About this StructureAbout this Structure
1TWR is a Single protein structure of sequence from Homo sapiens with VER and NO as ligands. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of ferrous and ferrous-NO forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage., Lad L, Ortiz de Montellano PR, Poulos TL, J Inorg Biochem. 2004 Nov;98(11):1686-95. PMID:15522396
Page seeded by OCA on Mon Nov 12 19:28:57 2007