1oqh
From Proteopedia
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'''Crystal Structure of the R124A mutant of the N-lobe human transferrin''' | '''Crystal Structure of the R124A mutant of the N-lobe human transferrin''' | ||
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[[Category: He, Q..Y.]] | [[Category: He, Q..Y.]] | ||
[[Category: Mason, A B.]] | [[Category: Mason, A B.]] | ||
| - | [[Category: | + | [[Category: Anion binding]] |
| - | [[Category: | + | [[Category: Iron binding]] |
| - | [[Category: | + | [[Category: Transferrin mutagenesis]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:09:39 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 01:09, 3 May 2008
Crystal Structure of the R124A mutant of the N-lobe human transferrin
Overview
Human transferrin is a serum protein whose function is to bind Fe(3+) with very high affinity and transport it to cells, for delivery by receptor-mediated endocytosis. Structurally, the transferrin molecule is folded into two globular lobes, representing its N-terminal and C-terminal halves, with each lobe possessing a high-affinity iron binding site, in a cleft between two domains. Central to function is a highly conserved set of iron ligands, including an aspartate residue (Asp63 in the N-lobe) that also hydrogen bonds between the two domains and an arginine residue (Arg124 in the N-lobe) that binds an iron-bound carbonate ion. To further probe the roles of these residues, we have determined the crystal structures of the D63E and R124A mutants of the N-terminal half-molecule of human transferrin. The structure of the D63E mutant, determined at 1.9 A resolution (R = 0.245, R(free) = 0.261), showed that the carboxyl group still binds to iron despite the larger size of the Glu side chain, with some slight rearrangement of the first turn of alpha-helix residues 63-72, to which it is attached. The structure of the R124A mutant, determined at 2.4 A resolution (R = 0.219, R(free) = 0.288), shows that the loss of the arginine side chain results in a 0.3 A displacement of the carbonate ion, and an accompanying movement of the iron atom. In both mutants, the iron coordination is changed slightly, the principal change being in each case a lengthening of the Fe-N(His249) bond. Both mutants also release iron more readily than the wild type, kinetically and in terms of acid lability of iron binding. We attribute this to more facile protonation of the synergistically bound carbonate ion, in the case of R124A, and to strain resulting from the accommodation of the larger Glu side chain, in the case of D63E. In both cases, the weakened Fe-N(His) bond may also contribute, consistent with protonation of the His ligand being an early intermediate step in iron release, following the protonation of the carbonate ion.
About this Structure
1OQH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional consequences of binding site mutations in transferrin: crystal structures of the Asp63Glu and Arg124Ala mutants of the N-lobe of human transferrin., Baker HM, He QY, Briggs SK, Mason AB, Baker EN, Biochemistry. 2003 Jun 17;42(23):7084-9. PMID:12795604 Page seeded by OCA on Sat May 3 04:09:39 2008
