Carboxypeptidase A: Difference between revisions

CPA from ''B. taurus'' has been  co-crystallized with two Zn²⁺ ions (Figure 1).  This structure has been deposited in the PDB database under the label [http://www.rcsb.org/pdb/explore/explore.do?structureId=1cpx 1CPX], which is a β-form of CPA.  The binding of only one Zn²⁺ ion is [http://en.wikipedia.org/wiki/Catalysis catalytic], while the binding of a second is [http://en.wikipedia.org/wiki/Reaction_inhibitor inhibitory].  These Zn²⁺ ions are connected to each other via a hydroxy-bridge (Figure 3) with a distance of 3.48 [http://en.wikipedia.org/wiki/%C3%85ngstr%C3%B6m Å].<ref name="CPA1" />  [[Image:1CPXhydroxybridge.png|150 px|right|thumb|Figure 3: Hydroxy-bridge between catalytic and inhibitory zinc ions.  The catalytic Zn²⁺ ion (shown in orange on the right) is bridged to the inhibitory Zn²⁺ ion (shown in orange on the left) by a OH^- (shown in red).]]  In the CPA structure containing only the catalytic Zn²⁺ ion ([http://www.rcsb.org/pdb/explore/explore.do?structureId=3cpa 3CPA]), a water molecule complexed to the zinc is able to be deprotonated by <scene name='69/694222/3cpas1subsiteglu270/1'>Glu270</scene> to allow for normal initiation of hydrolysis.  However, when the inhibitory Zn²⁺ ion is also present ([http://www.rcsb.org/pdb/explore/explore.do?structureId=1cpx 1CPX]), it occupies the physical space that would normally be occupied by the water molecule.  Thus, the inhibitory Zn²⁺ ion interacts with the carboxylate group of <scene name='69/694222/Glu270wiz/5'>Glu270</scene>.  The Glu270 now simply stabilizes the second zinc and is unable to perform its usual base catalyst role (Figure 4).