1xk0
From Proteopedia
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Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1
Contents |
Overview
Conserved glycines, Gly139 and Gly143, in the distal helix of human heme, oxygenase-1 (HO-1) provide the flexibility required for the opening and, closing of the heme active site for substrate binding and product, dissociation during HO-1 catalysis. Earlier mutagenesis work on human HO-1, showed that replacement of either Gly139 or Gly143 suppresses heme, oxygenase activity and, in the case of the Gly139 mutants, increases, peroxidase activity (Liu et al. in J. Biol. Chem. 275:34501, 2000). To, further investigate the role of the conserved distal helix glycines, we, have determined the crystal structures of the human HO-1 G139A mutant, the, G139A mutant in a complex with NO, and the G143H mutant at 1.88, 2.18 and, 2.08 A, respectively. The results confirm that fine tuning of the, previously noted active-site hydrogen-bonding network is critical in, determining whether heme oxygenase or peroxidase activity is observed.
Disease
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 Structure
1XK0 is a Single protein structure of sequence from Homo sapiens with HEM and NO as ligands. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.
Reference
Crystal structures of the G139A, G139A-NO and G143H mutants of human heme oxygenase-1. A finely tuned hydrogen-bonding network controls oxygenase versus peroxidase activity., Lad L, Koshkin A, de Montellano PR, Poulos TL, J Biol Inorg Chem. 2005 Mar;10(2):138-46. Epub 2005 Feb 3. PMID:15690204
Page seeded by OCA on Mon Nov 12 20:06:31 2007
