Phosphoglycerate Kinase

• Open file 1VPE

This is the crystal structure of a phosphoglycerate kinase molecule bound to the substrate 3-phosphoglycerate and an ATP analogue (AMP-PNP).  The enzyme is in its closed conformation.

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• Select hetero
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• Color CPK
• Select Mg
• Color Magenta
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Zoom in on the active site of the enzyme.  In addition to the substrates Mg²⁺ is also present.  The Mg is coordinated with the three phosphate groups on the ATP molecule.  Kinases (such as phosphoglycerate kinase) must shield their active sites from water to prevent hydrolysis of the ATP.  In 3PG this is accomplished by a "substrate-induced closure of the active-site cleft."  This conformational change begins with the binding of phosphoglycerate but the molecule does not completely close until both the phosphoglycerate and ATP are bound.

• Select lys197
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 Lys197 is also attracted to the C1-phosphate of 1,3-bisphosphoglycerate thus facilitating the closure of the two enzyme domains around the substrates.  It has also been proposed that the lys197 residue serves to stabilize the penta-coordinated transition state of the phosphoryl group.
 

• Select Arg62 or Asp200
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As the enzyme begins to close, a salt bridge forms between arg62 and asp200 to hold the two domains of the enzyme together in the closed conformation.  This salt bridge locks the enzyme in its closed conformation.

• Select 374-377
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• Color cpk

The actual catalysis of the reaction is facilitated by residues 374-377.  As the two domains of the enzyme begin to close upon each other several conformational changes occur which alter the relative orientations of these residues.  "Gly376 and gly377 become oriented towards the proposed position of the phosphate in the transition-state intermediate"  Also, the h-bond between Thr374 and glu174 breaks only to be reformed between glu174 and ser373.  Two h-bonds also forms between thr374 and arg36.