2bb5
From Proteopedia
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Structure of Human Transcobalamin in complex with Cobalamin
Contents |
Overview
Cobalamin (Cbl, vitamin B(12)) serves for two essential cofactors in, mammals. The pathway for its intestinal absorption, plasma transport, and, cellular uptake uses cell surface receptors and three Cbl-transporting, proteins, haptocorrin, intrinsic factor, and transcobalamin (TC). We, present the structure determination of a member of the mammalian, Cbl-transporter family. The crystal structures of recombinant human and, bovine holo-TCs reveal a two-domain architecture, with an N-terminal, alpha(6)-alpha(6) barrel and a smaller C-terminal domain. One Cbl molecule, in base-on conformation is buried inside the domain interface. Structural, data combined with previous binding assays indicate a domain motion in the, first step of Cbl binding. In a second step, the weakly coordinated ligand, H(2)O at the upper axial side of added H(2)O-Cbl is displaced by a, histidine residue of the alpha(6)-alpha(6) barrel. Analysis of amino acid, conservation on TC's surface in orthologous proteins suggests the location, of the TC-receptor-recognition site in an extended region on the, alpha(6)-alpha(6) barrel. The TC structure allows for the mapping of sites, of amino acid variation due to polymorphisms of the human TC gene., Structural information is used to predict the overall fold of haptocorrin, and intrinsic factor and permits a rational approach to the design of new, Cbl-based bioconjugates for diagnostic or therapeutic drug delivery.
Disease
Known diseases associated with this structure: Transcobalamin II deficiency OMIM:[275350]
About this Structure
2BB5 is a Single protein structure of sequence from Homo sapiens with B12 as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for mammalian vitamin B12 transport by transcobalamin., Wuerges J, Garau G, Geremia S, Fedosov SN, Petersen TE, Randaccio L, Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4386-91. Epub 2006 Mar 14. PMID:16537422
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