The Ottomans were not the first Islamic power to threaten the Byzantine Empire, and in fact the empire was by 1453 a hollowed out husk of its former glory. Successive waves of Turkish and Mongolian invasions had taken almost all of Anatolia out of Byzantine control, and the Ottomans had by this point conquered much of the empire’s former Balkan territory. Constantinople itself, whose population may once have been as high as 800,000 people (500,000 is more realistic), never recovered from the Fourth Crusade and the Black Death, and probably only housed about 50,000 by the middle of the 15th century. But the city had survived several sieges by Islamic armies (including the Ottomans) in the past, because of its seemingly impenetrable walls. Unfortunately for the Byzantines, this time the Ottomans brought some of the strongest cannons yet invented, cannons that were powerful enough to penetrate even those impenetrable walls.
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When I find myself in Constantinople, I like to take the light rail out to where the walls used to be and dream that Justinian’s Plague never happened.