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Publication Abstract from PubMed

We describe the 2.3 A X-ray structure of alpha1-micro-globulin (a1m), an abundant protein in human blood plasma, which reveals the beta-barrel fold typical for lipocalins with a deep pocket lined by four loops at its open rim. Loop #1 harbours the residue Cys34 that is responsible for covalent cross-linking with plasma IgA. A single disulfide bond between Cys72 and Cys169 connects the C-terminal segment to the beta-barrel as in many other lipocalins. The exposed imidazole side chains of His122 and His123 in loop #4 give rise to a double Ni2+-binding site together with a crystallographic neighbour. The closest structural relatives of a1m are the complement protein component C8gamma, the L-prostaglandin D synthase, and lipocalin 15, three other structurally characterized members of the lipocalin family in humans that have only distant sequence similarity. In contrast with these, a1m is initially expressed as a bifunctional fusion protein with the protease inhibitor bikunin. Neither the electron density nor ESI-MS provide evidence for a chromophore bound to the recombinant a1m, also known as "yellow-brown lipocalin". However, the three side chains of Lys92, Lys118, and Lys130 that were reported to be involved in covalent chromophore binding appear to be freely accessible to ligands accommodated in the hydrophobic pocket. A structural feature similar to the well known CP haem-binding motif indicates the presence of a haem-binding site within the loop region of a1m, which explains previous biochemical findings and supports a physiological role in haem scavenging as well as redox-mediated detoxification.

The crystal structure of human alpha1-microglobulin reveals a potential haem-binding site.,Meining W, Skerra A Biochem J. 2012 Apr 19. PMID:22512701^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.