Organisation, who were on their way to a rally organised to mark Yum-al-Quds - which is observed on the last Friday of the month of Ramzan to show solidarity with Palestinians, were fired at by unidentified gunmen.
At least five persons were injured in the shooting, witnesses said.
Minutes later, a bus carrying members of the Imamia Students Organisation, a body of Shia Muslims, was targeted with a remote-controlled explosive device near Safari Park area in Karachi.
The bus was partially destroyed as a result of the blast, which also hit over half a dozen cars and motorcycles.
One person was killed instantly, witnesses and police said. Another person died at the hospital.
Officials at nearby hospitals said they had received 14 injured people.
Police officials and witnesses said most of the injured were hit by ball bearings packed into the bomb.
The gun-and-bomb attack came a day after masked gunmen pulled out 25 Shia Muslims from three buses and shot them dead in Naran Valley of Khyber-Pakhtunkhwa province.
Edited By Cen Fox Post Team
