1TKL

Yeast Oxygen-Dependent Coproporphyrinogen Oxidase

Summary for 1TKL

• Entry DOI: 10.2210/pdb1tkl/pdb
• Related: 1TK1 1TLB
• Descriptor: Coproporphyrinogen III oxidase (2 entities in total)
• Functional Keywords: coproporphyrinogen oxidase, heme biosynthesis, enzyme, oxidoreductase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cytoplasm: P11353
• Total number of polymer chains: 2
• Total formula weight: 75070.46

Authors

Phillips, J.D.,Whitby, F.G.,Warby, C.A.,Labbe, P.,Yang, C.,Pflugrath, J.W.,Ferrara, J.D.,Robinson, H.,Kushner, J.P.,Hill, C.P. (deposition date: 2004-06-08, release date: 2004-07-20, Last modification date: 2024-02-14)

Primary citation

Phillips, J.D.,Whitby, F.G.,Warby, C.A.,Labbe, P.,Yang, C.,Pflugrath, J.W.,Ferrara, J.D.,Robinson, H.,Kushner, J.P.,Hill, C.P.
Crystal Structure of the Oxygen-dependant Coproporphyrinogen Oxidase (Hem13p) of Saccharomyces cerevisiae
J.Biol.Chem., 279:38960-38968, 2004

PubMed Abstract: Coproporphyrinogen oxidase (CPO) is an essential enzyme that catalyzes the sixth step of the heme biosynthetic pathway. Unusually for heme biosynthetic enzymes, CPO exists in two evolutionarily and mechanistically distinct families, with eukaryotes and some prokaryotes employing members of the highly conserved oxygen-dependent CPO family. Here, we report the crystal structure of the oxygen-dependent CPO from Saccharomyces cerevisiae (Hem13p), which was determined by optimized sulfur anomalous scattering and refined to a resolution of 2.0 A. The protein adopts a novel structure that is quite different from predicted models and features a central flat seven-stranded anti-parallel sheet that is flanked by helices. The dimeric assembly, which is seen in different crystal forms, is formed by packing of helices and a short isolated strand that forms a beta-ladder with its counterpart in the partner subunit. The deep active-site cleft is lined by conserved residues and has been captured in open and closed conformations in two different crystal forms. A substratesized cavity is completely buried in the closed conformation by the approximately 8-A movement of a helix that forms a lid over the active site. The structure therefore suggests residues that likely play critical roles in catalysis and explains the deleterious effect of many of the mutations associated with the disease hereditary coproporphyria.

PubMed: 15194705
DOI: 10.1074/jbc.M406050200

Experimental method

X-RAY DIFFRACTION (2 Å)