You'll have to have SED installed on the client and in the PGP messenging you'll have to list the mail server and the encryption server. You can setup mail policy for auto encryption based on rules on the SEMS server.
Additional info:
The Lotus Domino would connect to the SEMS on an outbound connector, SEMS mail proxy would outbound to the gateway or Spam filter (if applys)
The SEMS mail proxy for the Inbound would point to the Lotus Domino server. (SMTP unified)
Managed Domain on the SEMS would be set. (Most of this is setup in installation of the SEMS server)
DNS and MX records would have to be created.
Here is an article of what is supported:
http://www.symantec.com/business/support/index?page=content&id=TECH148838