1lfg
Structure of diferric human lactoferrin
Structural highlights
FunctionTRFL_HUMAN Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.[1] [2] Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration.[3] [4] Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.[5] [6] The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.[7] [8] Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.[9] [10] 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 PubMedThe three-dimensional structure of the diferric form of human lactoferrin has been refined at 2.2 A resolution, using synchrotron data combined with a lower resolution (3.2 A) diffractometer data set. Following restrained least-squares refinement and model rebuilding the final model comprises 5330 protein atoms (691 residues), 2Fe(3+) and 2CO(3)(2-) ions, 469 solvent molecules and 98 carbohydrate atoms (eight sugar residues). Root-mean-square deviations from standard geometry are 0.015 A for bond lengths and 0.038 A for angle (1-3) distances, and the final crystallographic R-factor is 0.179 for all 39 113 reflections in the resolution range 8.0-2.2 A. A close structural similarity is seen between the two lobes of the molecule, with differences mainly in loops and turns. The two binding sites are extremely similar, the only apparent differences being a slightly more asymmetric bidentate binding of the carbonate ion to the metal, and a slightly longer Fe-O bond to one of the Tyr ligands, in the N-lobe site relative to the C-lobe site. Distinct differences are seen in the interactions made by two cationic groups, Arg210 and Lys546, behind the iron site, and these may influence the stability of the two metal sites. Analysis of interdomain and interlobe interactions shows that these are few in number which is consistent with the known flexibility of the molecule with respect to domain and lobe movements. Internal water molecules are found in discrete sites and in two large clusters (in the two interdomain clefts) and one tightly bound water molecule is present 3.8 A from the Fe atom in each lobe. The carbohydrate is weakly defined and has been modelled to a limited extent; two sugar residues of the N-lobe glycan and six of the C-lobe glycan. Only one direct protein-carbohydrate contact can be found. Structure of human diferric lactoferrin refined at 2.2 A resolution.,Haridas M, Anderson BF, Baker EN Acta Crystallogr D Biol Crystallogr. 1995 Sep 1;51(Pt 5):629-46. PMID:15299793[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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