Smith and Jacques Kallis made solid half-centuries in a partnership of 150 to rescue their side from deep trouble at 10 for two but both fell in quick succession before bad light ended play early with England on top.
"The run out was especially frustrating, but that sort of thing happens often in cricket and you just have to accept it and get on with the game."
Smith fell for 75 after playing a defensive stroke to a ball from Graham Onions, AB de Villiers impetuously charging through for a single before sending his captain back and leaving him stranded. The South Africans scored only 15 runs in the first 13 overs as England made light of losing the toss by removing Ashwell Prince and Hashim Amla.
But Kallis increased the scoring rate in compiling his 52nd Test half-century, hitting seven fours and looking poised to score another century when he was deceived by off-spinner Graeme Swann and edged the ball to Paul Collingwood at slip.
De Villiers incurred his captain's wrath three overs later and Onions gained reward for his accurate seam bowling by trapping JP Duminy lbw for four with a fine swinging delivery.
"All of a sudden three big wickets fell to swing the game back in our favour," Onions said.
"We feel we finished strongly and the way we bowled and fielded, we deserved a bit of luck going our way. The run out was also a key part of the game because if Graeme Smith had been not out, it would have made a big difference."
De Villiers, on eight, and Mark Boucher on one, were the not out batsmen at the close.
South Africa made a poor start after winning the toss.
Seamer James Anderson made a good-length delivery leap off the pitch at Prince and the left-hander sent an edge fizzing to Swann at third slip.
Amla tried to play a straight delivery from Stuart Broad on the on-side and was trapped lbw for two. England's fast bowlers held sway for the first hour on a pitch that always threatened the batsmen with its pace and bounce. Smith was struck a painful blow on the left hand by Anderson but he and Kallis settled in to take their side to 67 for two at lunch and 151 for two at tea. The first Test of the four-match series ended in a draw.
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