1lz6

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1lz6, resolution 1.8Å

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STRUCTURAL AND FUNCTIONAL ANALYSES OF THE ARG-GLY-ASP SEQUENCE INTRODUCED INTO HUMAN LYSOZYME

Contents

Overview

To determine the functional conformation of the Arg-Gly-Asp (RGD), sequence, we have constructed mutant proteins by inserting 4-12 amino acid, residues from the RGD region of human fibronectin between Val74 and Asn75, of human lysozyme. RGDS-, GRGDSP-, TGRGDSPA-, VTGRGDSPAS-, and, AVTGRGDS-PASS-introduced mutant lysozymes were expressed in yeast, purified, and designated as RGD4, -6, -8, -10, and -12, respectively., Using baby hamster kidney cells, RGD8, RGD10, and RGD12 were shown to, possess high cell adhesion activity nearly equal to 10% of human, vitronectin activity. RGD4 and RGD6 exhibited somewhat lower cell adhesion, activity. The activities of these mutant proteins were inhibited by the, addition of either GRGDSP peptide or polyclonal antibody against, vitronectin receptor, as was the case for the vitronectin activity. The, results suggest that the cell adhesion signals are transduced to cells, through the interaction with the vitronectin receptor. The, three-dimensional structures of RGD4 and RGD8 were determined at 1.8-A, resolution by x-ray crystallography. A model of the inserted region in, RGD4 could be built in the electron density map, but the positions of the, preceding residues, Ala73-Val74, were uncertain. The inserted region in, RGD8 did not demonstrate continuous electron densities. The results, suggest that these RGD sequence-containing regions are highly flexible and, that such flexibility could allow the conformation of the RGD regions to, be induced to fit into the binding pocket of the integrin receptor.

Disease

Known diseases associated with this structure: Amyloidosis, renal OMIM:[153450], Microphthalmia, syndromic 1 OMIM:[309800]

About this Structure

1LZ6 is a Single protein structure of sequence from Homo sapiens with CL as ligand. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.

Reference

Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme., Yamada T, Matsushima M, Inaka K, Ohkubo T, Uyeda A, Maeda T, Titani K, Sekiguchi K, Kikuchi M, J Biol Chem. 1993 May 15;268(14):10588-92. PMID:8486712

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