PDBsum entry 1ovc

Transferase

PDB id: 1ovc

Contents

Protein chain

295 a.a.

Ligands

AQ4

Theoretical model

PDB id:

1ovc

Name:

Transferase

Title:

Theoretical model of tyrosine kinase domain of receptor protein-tyrosine kinase erbb-2 precursor (c-erbb-2)

Structure:

Receptor protein-tyrosine kinase erbb-2. Chain: a. Fragment: residues 1-295. Synonym: tyrosine kinase domain. Ec: 2.7.1.112

Source:

Homo sapiens. Human

Authors:

G.Raana,R.Khurshid,A.Salim,M.A.Ather

Key ref:

P.F.Lindley et al. (1993). The mechanism of iron uptake by transferrins: the structure of an 18 kDa NII-domain fragment from duck ovotransferrin at 2.3 A resolution. Acta Crystallogr D Biol Crystallogr, 49, 292-304. PubMed id: 15299534 DOI: 10.1107/S0907444992012101

Date:

26-Mar-03 Release date: 08-Apr-03

Protein chain

P04626  (ERBB2_HUMAN) -  Receptor tyrosine-protein kinase erbB-2 from Homo sapiens

Seq: 1255 a.a.

Struc: 295 a.a.

DOI no: 10.1107/S0907444992012101

Acta Crystallogr D Biol Crystallogr 49:292-304 (1993)

PubMed id: 15299534

The mechanism of iron uptake by transferrins: the structure of an 18 kDa NII-domain fragment from duck ovotransferrin at 2.3 A resolution.

P.F.Lindley, M.Bajaj, R.W.Evans, R.C.Garratt, S.S.Hasnain, H.Jhoti, P.Kuser, M.Neu, K.Patel, R.Sarra, R.Strange, A.Walton.

ABSTRACT

The molecular structure of an iron-containing 18 kDa fragment of duck ovotransferrin, obtained by proteolysis of the intact protein, has been elucidated by protein crystallographic techniques at 2.3 A resolution. This structure supports a mechanism of iron uptake in the intact protein whereby the binding of the synergistic (bi)carbonate anion is followed by binding of the metal with the lobe in the open configuration. These stages are then followed by domain closure in which the aspartic acid residue plays a further key role, by forming an interdomain hydrogen-bond interaction in addition to serving as a ligand to the iron. This essential dual role is highlighted by model building studies on the C-terminal lobe of a known human variant. In this variant a mutation of a glycine by an arginine residue enables the aspartic acid to form an ion pair and reduce its effectiveness for both metal binding and domain closure. The X-ray structure of the 18 kDa fragment strongly suggests that the histidine residue present at the iron binding site of the intact protein and arising from the second interdomain connecting strand has been removed during the preparative proteolysis.

Selected figure(s)

Figure 3.
Fig. 3. ariation of the R factor during the course of the refinement. h refinement wa carried out in eight stges, each consisting of a moel-building session and restrained last- squares o simulated-annealing refinement.

Figure 12.
Fig. 12. The hypothetical C-terminal iron binding site in the human variant tranferrin. (a) A stereoview of the C-lobe iron binding site in the native serum protein. (h) A stereoview of the C-lobe iron binding site in the variant. Arg394 forms twin- contact ion pair with Asp392 drawing it away from the ron. Asp392 retains its hydrogen bond with the amide of residue 394 and the tye 1 turn remains intact.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1993, 49, 292-304) copyright 1993.

Figures were selected by an automated process.