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The first structure from the SOUL/HBP family of heme-binding proteins, murine P22HBP. J Biol Chem 2006 Oct 20;281(42):31553-61

Date

08/15/2006

Pubmed ID

16905545

DOI

10.1074/jbc.M605988200

Scopus ID

2-s2.0-33846009114   19 Citations

Abstract

Murine p22HBP, a 22-kDa monomer originally identified as a cytosolic heme-binding protein ubiquitously expressed in various tissues, has 27% sequence identity to murine SOUL, a heme-binding hexamer specifically expressed in the retina. In contrast to murine SOUL, which binds one heme per subunit via coordination of the Fe(III)-heme to a histidine, murine p22HBP binds one heme molecule per subunit with no specific axial ligand coordination of the Fe(III)-heme. Using intrinsic protein fluorescence quenching, the values for the dissociation constants of p22HBP for hemin and protoporphyrin-IX were determined to be in the low nanomolar range. The three-dimensional structure of murine p22HBP, the first for a protein from the SOUL/HBP family, was determined by NMR methods to consist of a 9-stranded distorted beta-barrel flanked by two long alpha-helices. Although homologous domains have been found in three bacterial proteins, two of which are transcription factors, the fold determined for p22HBP corresponds to a novel alpha plus beta fold in a eukaryotic protein. Chemical shift mapping localized the tetrapyrrole binding site to a hydrophobic cleft formed by residues from helix alphaA and an extended loop. In an attempt to assess the structural basis for tetrapyrrole binding in the SOUL/HBP family, models for the p22HBP-protoporphyrin-IX complex and the SOUL protein were generated by manual docking and automated methods.

Author List

Dias JS, Macedo AL, Ferreira GC, Peterson FC, Volkman BF, Goodfellow BJ

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Carrier Proteins
Heme
Hemeproteins
Hemin
Humans
Mice
Molecular Sequence Data
Protein Structure, Secondary
Protoporphyrins
Sequence Homology, Amino Acid
Tetrapyrroles
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46