Cyanide Binding and Heme Cavity Conformational Transitions in Drosophila melanogaster Hexacoordinate Hemoglobin

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• 作者：Daniele de Sanctis ; Paolo Ascenzi ; Alessio Bocedi ; Sylvia Dewilde ; Thorsten Burmester ; Thomas Hankeln ; Luc Moens ; Martino Bolognesi
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：August 22, 2006
• 年：2006
• 卷：45
• 期：33
• 页码：10054 - 10061
• 全文大小：469K
• 年卷期：v.45,no.33(August 22, 2006)
• ISSN：1520-4995

文摘

The reason for the presence of hemoglobin-like molecules in insects, such as Drosophilamelanogaster, that live in fully aerobic environments has yet to be determined. Heme endogenoushexacoordination (where HisE7 and HisF8 axial ligands to the heme Fe atom are both provided by theprotein) is a recently discovered mechanism proposed to modulate O₂ affinity in hemoglobins from differentspecies. Previous results have shown that D. melanogaster hemoglobin 1 (product of the glob1 gene)displays heme endogenous hexacoordination in both the ferrous and ferric states. Here we present kineticdata characterizing the exogenous cyanide ligand binding process, and the three-dimensional structure (at1.4 Å resolution) of the ensuing cyano-met D. melanogaster hemoglobin. Comparison with the crystalstructure of the endogenously hexacoordinated D. melanogaster hemoglobin shows that the transition tothe cyano-met form is supported by conformational readjustment in the CD-D-E region of the protein,which removes HisE7 from the heme. The structural and functional features of D. melanogaster hemoglobinare examined in light of previous results achieved for human and mouse neuroglobins and for humancytoglobin, which display heme endogenous hexacoordination. The study shows that, despite the ratherconstant value for cyanide association rate constants for the ferric hemoproteins, different distal siteconformational readjustments and/or heme sliding mechanisms are displayed by the known hexacoordinatehemoglobins as a result of exogenous ligand binding.