2pmv

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Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A ResolutionCrystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution

Structural highlights

2pmv is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IF_HUMAN Defects in GIF are the cause of hereditary intrinsic factor deficiency (IFD) [MIM:261000; also known as congenital pernicious anemia. IFD is an autosomal recessive disorder characterized by megaloblastic anemia.[1]

Function

IF_HUMAN Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.

Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.,Mathews FS, Gordon MM, Chen Z, Rajashankar KR, Ealick SE, Alpers DH, Sukumar N Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17311-6. Epub 2007 Oct 22. PMID:17954916[2]

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

References

  1. Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, Yurtsever Z, David KL, Faivre L, Ismail EA, Grasbeck R, de la Chapelle A. Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4130-3. Epub 2005 Feb 28. PMID:15738392 doi:0500517102
  2. Mathews FS, Gordon MM, Chen Z, Rajashankar KR, Ealick SE, Alpers DH, Sukumar N. Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution. Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17311-6. Epub 2007 Oct 22. PMID:17954916

2pmv, resolution 2.60Å

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