PDBsum entry 3ib0

Metal binding protein

PDB id: 3ib0

Contents

Protein chain

341 a.a. *

Ligands

NAG-NAG

NAG-NAG-MAN-MAN-MAN

NAG-NAG-MAN-MAN-MAN-MAN

CO3

DIF

SO4 ×2

EOH

Metals

_FE

_ZN ×2

Waters ×509

* Residue conservation analysis

PDB id:

3ib0

Name:

Metal binding protein

Title:

Structural basis of the prevention of nsaid-induced damage of the gastrointestinal tract by c-terminal half (c-lobe) of bovine colostrum protein lactoferrin: binding and structural studies of c- lobe complex with diclofenac

Structure:

Lactotransferrin. Chain: a. Fragment: unp residues 361-705. Synonym: lactoferrin, lactoferricin-b, lfcin-b. Ec: 3.4.21.-

Source:

Bos taurus. Bovine. Organism_taxid: 9913

Resolution:

1.40Å R-factor: 0.204 R-free: 0.219

Authors:

R.Mir,N.Singh,M.Sinha,S.Sharma,P.Kaur,A.Srinivasan,T.P.Singh

Key ref:

R.Mir et al. (2009). The structural basis for the prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal tract damage by the C-lobe of bovine colostrum lactoferrin. Biophys J, 97, 3178-3186. PubMed id: 20006955

Date:

15-Jul-09 Release date: 11-Aug-09

Supersedes:

3hwv

Protein chain

P24627  (TRFL_BOVIN) -  Lactotransferrin from Bos taurus

Seq: 708 a.a.

Struc: 341 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.21.- - ?????

Biophys J 97:3178-3186 (2009)

PubMed id: 20006955

The structural basis for the prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal tract damage by the C-lobe of bovine colostrum lactoferrin.

R.Mir, N.Singh, G.Vikram, R.P.Kumar, M.Sinha, A.Bhushan, P.Kaur, A.Srinivasan, S.Sharma, T.P.Singh.

ABSTRACT

Nonsteroidal antiinflammatory drugs (NSAIDs), due to their good efficacy in the treatment of pain, inflammation, and fever, are among the most prescribed class of medicines in the world. The main drawback of NSAIDs is that they induce gastric complications such as peptic ulceration and injury to the intestine. Four NSAIDs, indomethacin, diclofenac, aspirin, and ibuprofen were selected to induce gastropathy in mouse models. It was found that the addition of C-terminal half of bovine lactoferrin (C-lobe) reversed the NSAID-induced injuries to the extent of 47-70% whereas the coadministration of C-lobe prevented it significantly. The C-lobe was prepared proteolytically using serine proteases. The binding studies of C-lobe with NSAIDs showed that these compounds bind to C-lobe with affinities ranging from 2.6 to 4.8 x 10(-4) M. The complexes of C-lobe were prepared with the above four NSAIDs. All four complexes were crystallized and their detailed three-dimensional structures were determined using x-ray crystallographic method. The structures showed that all the four NSAID molecules bound to C-lobe at the newly identified ligand binding site in C-lobe that is formed involving two alpha-helices, alpha10 and alpha11. The ligand binding site is separated from the well known iron binding site by the longest and the most stable beta-strand, betaj, in the structure. Similar results were also obtained with the full length lactoferrin molecule. This novel, to our knowledge, binding site in C-lobe of lactoferrin shows a good complementarity for the acidic and lipophilic compounds such as NSAIDs. We believe this indicates that C-lobe of lactoferrin can be exploited for the prevention of NSAID-induced gastropathy.