This trade detracted from the resources of the Sultan, and spelt ruin to the seaports of Italy. In 1503 the Sultan addressed a letter to the Pope in which he threatened destruction to the Holy Places, including the Holy Sepulchre and the convent of Sinai, if the Portuguese were not interfered with. But King Manuel of Portugal induced the Pope to ignore the letter, and, on his side, offered spicery free of duty to the Venetians, if they fetched it at Lisbon, instead of Alexandria. But the Venetians, averse to the change, persuaded the Sultan to set up a direct communication by boat between Suez and India, and a tower was accordingly built to fortify Suez. Tur was passed over; its days as a port on the way to India were drawing to a close, for the Portuguese were determined to monopolise the trade with India. They seized a boat coming from Egypt with the 24,000 ducats it contained. They fitted out a war fleet (1504) which enforced their superior claims in India, and attacked all other shipping. In 1509 they entered the Red Sea with their war fleet, and interfered with the pilgrims to Mecca. It was in vain that the Venetians, whose annual turn-over at Alexandria fell from 600,000 to 100,000 ducats in 1511, pleaded with the Sultan to diminish the tax on Eastern goods, so as to enable them to compete with the Portuguese. The Sultanate was at the mercy of short-sighted and intriguing emirs, and was weakening. The conquering Ottoman Turk was steadily gaining ground. There had been rejoicing at Cairo when Constantinople, in 1453, fell to the power of Islam, but the struggle for supremacy soon afterwards began between the Egyptian and the Ottoman Sultanate. In 1516 the Ottoman Sultan Selim († 1520) occupied Damascus, and in the following year he advanced along the road of El Arish with wheeled transport. After defeating the Mameluks at Radunieh in 1517, he led his disciplined janissaries into Cairo, where he appropriated the sacred banner of Islam and the relics, which he removed to Constantinople. In the meantime the shipping languished even at Suez. Odoardo Barbosa, who was sent to Egypt to report on matters of navigation to the merchants of Italy in 1516, mentioned Suez as the station for spicery, but added that the traffic had almost ceased.[283] Certainly the Ottoman Sultan, roused to the needs of the hour, made the attempt to facilitate the transit of Eastern goods by cutting through the isthmus of Suez. He also built a castle at Suez in order to defend himself against the Portuguese. But the centre of the Ottoman rule was no longer Cairo, but Constantinople, to which the wealthy more and more migrated. Egypt was placed under a pasha, who was appointed at Constantinople, and who was frequently changed so as to anticipate any scheme on his part of making himself into an independent ruler. Cairo retained its university and remained a centre of learning; its halcyon days as a centre of art and luxury were at an end.