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2bb5
From Proteopedia
| 2bb5, resolution 3.20Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | |||||||||
| Gene: | TCN2, TC2 (Homo sapiens) | ||||||||
| Domains: | Cobalamin_bind | ||||||||
| Related: | 2bb6, 2bbc | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure of Human Transcobalamin in complex with Cobalamin
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2BB5 is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Wuerges J, Garau G, Geremia S, Fedosov SN, Petersen TE, Randaccio L. Structural basis for mammalian vitamin B12 transport by transcobalamin. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4386-91. Epub 2006 Mar 14. PMID:16537422
Page seeded by OCA on Tue Feb 17 15:45:39 2009
