The structure of murine neuroglobin: Novel pathways for ligand migration and binding.
Neuroglobin, a recently discovered globin predominantly expressed in neuronal tissue of vertebrates, binds small, gaseous ligands at the sixth coordination position of the heme iron. In the absence of an exogenous ligand, the distal histidine (His64) binds to the heme iron in the ferrous and ferric states. The crystal structure of murine ferric (met) neuroglobin at 1.5 A reveals interesting features relevant to the ligand binding mechanism. Only weak selectivity is observed for the two possible heme orientations, the occupancy ratio being 70:30. Two small internal cavities are present on the heme distal side, which enable the His64(E7) side chain to move out of the way upon exogenous ligand binding. Moreover, a third, huge cavity (volume approximately 290 A3) connecting both sides of the heme, is open towards the exterior and provides a potential passageway for ligands. The CD and EF corners exhibit substantial flexibility, which may assist ligands in entering the protein and accessing the active site. Based on this high-resolution structure, further structure-function studies can be planned to elucidate the role of neuroglobin in physiological responses to hypoxia.
Vallone
Beatrice
B
Department of Biochemical Sciences, University of Rome La Sapienza, Rome, Italy. beatrice.vallone@uniroma1.it
Nienhaus
Karin
K
Brunori
Maurizio
M
Nienhaus
G Ulrich
GU
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005914:Globins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D018583:Pliability; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D008024:Ligands; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D006418:Heme; D005914:Globins