Nothing really wrong about your code (regMySoft needs to be static though), but you may want to check for the existance of the key, and if you need to create it, the registry key needs to have write permissions.

    public static class Config
    {
        private static RegistryKey key = Registry.LocalMachine.OpenSubKey("SOFTWARE\\MySoft", true);
        private static RegistryKey softwareKey = Registry.LocalMachine.OpenSubKey("SOFTWARE", true);

        public static string MailServer
        {
            get
            {
                if (key == null)
                {
                    softwareKey.CreateSubKey("MySoft");
                    key = softwareKey.OpenSubKey("MySoft", true);
                    key.SetValue("mailServer", "Default value");
                }
                return key.GetValue("mailServer").ToString();
            }
            set { key.SetValue("mailServer", value); }
        }
    }

More something like this?

    public class Config
    {
        private static RegistryKey regMySoft =
                Registry.LocalMachine.OpenSubKey("SOFTWARE\\MySoft");

        public static String MailServer
        {
            get
            {
                return regMySoft.GetValue("mailServer").ToString();
            }
            set
            {
                regMySoft.SetValue("mailServer", value);
            }
        }
    }
 }

x = Config.MailServer;
Config.MailServer = x;