Hey Tony! It sounds like you might just be missing an HTTP/HTTPS binding for your SmarterMail site in IIS. Can you check that to make sure you have one listed there for that hostname and using the appropriate IP address? If its setup to listen on the wrong IP this could cause a 404 as well, so you'll want to double-check all of those settings to be safe. Let me know what you find!
Kyle Kerst
System/Network Administrator
SmarterTools Inc.
(877) 357-6278
www.smartertools.com