Catechol, a Urinary Ngal Binding Siderophore

NGAL (siderocalin), is a carrier protein that is expressed by neutrophils and by epithelia stimulated by iron, hypoxia and growth factors. Functionally NGAL binds enterochelin:Fe, a bacterial siderophore, but since NGAL is expressed in sterile forms of renal failure, NGAL may bind additional organic chemicals. To identify these molecules, we took both a candidate molecule approach as well as purified from 400 liters of human urine endogenous NGAL siderophores. We have now established that catechol solubilized iron, binds NGAL with a spectral shift similar to enterochelin, retains iron in an NGAL complex, even after days of washing, and demonstrated crystallographic evidence of occupancy of the NGAL calyx. This is the first report of Ngal:mammalian siderophore complex as the principal urinary non-transferrin bound iron pool carrier. References: [1] Yang J, et al. (2002) Mol. Cell 10: 1045–1056. [2] Mori K, et al. (2005) J. Clin. Invest. 115: 610–621.