Determination of the nature of the heme environment in nitrosyl indoleamine 2,3-dioxygenase using Multiple-scattering analyses of X-ray absorption fine structure.
Multiple-scattering analysis of X-ray absorption fine structure data on the NO adducts of indoleamine 2,3-dioxygenase (IDO) and analysis of X-ray absorption near-edge structure (XANES) have provided the first direct structural information about the iron center for this ubiquitous mammalian metalloprotein. The IDO(II)NO adduct, which is likely to play a physiological role in the immune system, differs from similar adducts such as Mb(II)NO and Lb(II)NO in that the Fe-His bond is essentially broken. At 10 K, the Fe-N(p)(av) bond length = 2.00(2) A, Fe-NO bond length = 1.75 A, and angle = 140 degrees, which are typical of five-coordinate Fe(II)NO species. The XANES is also closer to that of five-coordinate model complexes than six-coordinate species. In addition to the Fe(II)NO species, there was a minor component of the Fe(III)NO adduct because of incomplete reduction of the Fe(II) species. This was also a five-coordinate center and consists of a linear Fe(II)NO(+) moiety with the Fe-N(p)(av) bond length = 2.00(2) A, Fe-NO bond length = 1.63(3) A, and angle = 179 degrees. The results indicate that both the blocking of the heme site to O(2) binding and conformational changes induced by breaking the Fe-N(epsilon) bond may be important mechanisms by which NO inhibits IDO in vitro and in vivo.
Aitken
Jade B
JB
Centre for Structural Biology and Structural Chemistry, and Centre for Heavy Metals Research, School of Chemistry, The University of Sydney, New South Wales 2006, Australia.
Thomas
Sushila E
SE
Stocker
Roland
R
Thomas
Shane R
SR
Takikawa
Osamu
O
Armstrong
Robert S
RS
Lay
Peter A
PA
D001665:Binding Sites; D018360:Crystallography, X-Ray; D005583:Fourier Analysis; D006418:Heme / Q000737:chemistry*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007501:Iron / Q000737:chemistry; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D012542:Scattering, Radiation; D013052:Spectrometry, X-Ray Emission; D013056:Spectrophotometry, Ultraviolet; D014366:Tryptophan Oxygenase / Q000737:chemistry*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009569:Nitric Oxide; D006418:Heme; D007501:Iron; D014366:Tryptophan Oxygenase; D009584:Nitrogen; D010100:Oxygen