1LMT

STRUCTURE OF A CONFORMATIONALLY CONSTRAINED ARG-GLY-ASP SEQUENCE INSERTED INTO HUMAN LYSOZYME

Summary for 1LMT

• Entry DOI: 10.2210/pdb1lmt/pdb
• Related PRD ID: PRD_900017
• Descriptor: HUMAN LYSOZYME, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: hydrolase (o-glycosyl)
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16041.89

Authors

Matsushima, M.,Song, H. (deposition date: 1995-01-13, release date: 1995-03-31, Last modification date: 2024-11-20)

Primary citation

Yamada, T.,Song, H.,Inaka, K.,Shimada, Y.,Kikuchi, M.,Matsushima, M.
Structure of a conformationally constrained Arg-Gly-Asp sequence inserted into human lysozyme.
J.Biol.Chem., 270:5687-5690, 1995

PubMed Abstract: To examine the effect of a conformational constraint introduced into the Arg-Gly-Asp (RGD) sequence on cell adhesion activity, we constructed a mutant protein by inserting an RGD-containing sequence flanked by two Cys residues between Val74 and Asn75 of human lysozyme. The CRGDSC-inserted lysozyme was expressed in yeast, purified, and designated as Cys-RGD4. Using baby hamster kidney cells, Cys-RGD4 was shown to possess even higher cell adhesion activity than that of the RGDS-inserted lysozyme, RGD4. The Cys-RGD4 protein was co-crystallized with a lysozyme inhibitor, tri-N-acetylchitotriose, and the three-dimensional structure was determined at 1.6-A resolution by x-ray crystallography. In contrast to RGD4, the inserted RGD-containing region of Cys-RGD4 was well defined. The structural analysis revealed that the two inserted Cys residues form a new disulfide bond in Cys-RGD4, as expected, and that the RGD region assumes a type II' beta-turn conformation of Gly-Asp with a hydrogen bond between the C = O of Arg and the H-N of Ser. In addition, it was confirmed that two more hydrogen bonds are present in the RGD region of the Cys-RGD4 lysozyme. These results suggest that the conformation of the RGD-containing region is rigid and stable in the Cys-RGD4 molecule and that the type II' beta-turn structure of RGD is essential for binding to integrins with high affinity.

PubMed: 7890692
DOI: 10.1074/jbc.270.11.5687

Experimental method

X-RAY DIFFRACTION (1.6 Å)