The blast occurred outside the wall that protects the checkpoint
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A suicide bomber killed five Iraqis and a US soldier outside an entrance to the headquarters of the US-led coalition.
Several people were hurt, including two US soldiers said to be in a "very serious condition" after the first bomb to target coalition offices for weeks.
An officer said the attacker drove up to a checkpoint in central Baghdad and detonated explosives.
Just before midnight two soldiers were killed and two were wounded when a roadside bomb exploded in the city.
Central Baghdad was rocked by a third blast later on Thursday morning.
Witnesses said two Iraqis were injured when the bomb exploded in a commercial area, shattering glass and damaging vehicles.
Meanwhile, 10 members of a radical Shia militia were reportedly killed during the night in raids by US forces in Baghdad's slum district of Sadr city.
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We went outside and we saw one of the cars waiting to be checked on fire
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One US soldier was wounded during the clashes in the area which is a hotbed of support for Shia cleric Moqtada al-Sadr
"We will continue to hunt down Sadr's militia as intelligence comes in. We go where the intelligence takes us," said a US military official quoted by AFP.
In the city of Baquba, north of Baghdad, the offices of a Kurdish political party were reportedly destroyed in a bombing that also wounded four people.
Howling sirens
Several cars were queuing for checks before entering the heavily-fortified headquarters - the so called Green Zone - when the car blast went off.
A black column of smoke rose into the air as sirens howled at the scene.
"We saw a car on fire," Mohammed Talum, who lives close to the bridge, told AFP after the 0700 (0300 GMT) blast.
A local bakery owner, Qays Mohamed, told Reuters he had heard a "very big explosion".
"We went outside and we saw one of the cars waiting to be checked on fire," he said.
Colonel John Murray said at least 10 vehicles had been affected by the blast.
The 14 July suspension bridge where the explosion occurred is used only by coalition forces and employees of the US administration.
A car bomb outside another entrance in January killed at least 20 Iraqi workers waiting to get into the compound.