Carboxypeptidase A: Difference between revisions

<StructureSection load='1cpx' size='340' side='right' scene='69/694222/1cpx_default/1'>

<scene name='69/694222/1cpx_default/1'>Carboxypeptidase A (peptidyl-L-amino acid hydrolase, EC 3.4.17.1, often abbreviated CPA)</scene> is a metallo[http://en.wikipedia.org/wiki/Exopeptidase exopeptidase] whose biological function is to cleave the [http://en.wikipedia.org/wiki/C-terminus C-terminal] amino acid residue from polypeptide substrates.<ref name="CPA1">Bukrinsky JT, Bjerrum MJ, Kadziola A. 1998. Native carboxypeptidase A in a new crystal environment reveals a different conformation of the important tyrosine 248. ''Biochemistry''. 37(47):16555-16564. [http://pubs.acs.org/doi/abs/10.1021/bi981678i DOI: 10.1021/bi981678i]</ref>  Specifically, CPA is one member of a large group of Zn²⁺ [http://en.wikipedia.org/wiki/Metalloprotein#Metalloenzymes metalloenzymes] that carries out the hydrolysis of C-terminal polypeptide residues through the [http://en.wikipedia.org/wiki/Deprotonation deprotonation] of a water molecule that is coordinated to the Zn²⁺ ion in the enzyme's [http://en.wikipedia.org/wiki/Active_site active site].<ref name="CPA2">Christianson DW, Lipscomb WN. 1989. Carboxypeptidase A. ''Acc. Chem. Res.'' 22:62-69.</ref>  CPA consists of a single polypeptide chain that contains 307 amino acids.  Produced in the pancreas, CPA itself must first be modified by [http://en.wikipedia.org/wiki/Trypsin trypsin] and [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin] in order to achieve an active form that serves its biological function.<ref name="CPA1" />  Although different biologically active forms of CPA are found across different species, including humans, much research has investigated bovine pancreatic zinc carboxypeptidase A.  [http://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] has demonstrated that bovine CPA has the ability to bind two Zn²⁺ ions in its active site, in which the binding of one Zn²⁺ is catalytic (shown in cyan), while the binding of a second Zn²⁺ inhibits the hydrolysis reaction mechanism (shown in red) (Figure 1).<ref name="CPA1" />  An example of a crystal structure for active CPA (one zinc bound) has been deposited in the [http://www.rcsb.org/pdb/home/home.do Protein Data Bank (PDB) database] as [http://www.rcsb.org/pdb/explore/explore.do?structureId=3cpa 3CPA].  An inhibited CPA (two zincs bound) has been deposited under the label [http://www.rcsb.org/pdb/explore/explore.do?structureId=1cpx 1CPX].

Bovine CPA exists as a single unit with [http://en.wikipedia.org/wiki/Molecular_symmetry C1 symmetry] in the pancreatic physiological environment.  According to [http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=3CPA structural information] deposited in the PDB database, the single polypeptide chain of CPA contains a mixture of <scene name='69/694222/3cpasecondarystructure/1'>α-helices and β-sheets</scene>, of which there are a total of 11 helices (one [http://en.wikipedia.org/wiki/310_helix 3₁₀], eight [http://en.wikipedia.org/wiki/Alpha_helix 3.6₁₃]) and ten [http://en.wikipedia.org/wiki/Beta_sheet β-strands].  The helices are shown in magenta, and the β-strands are displayed in yellow.  A [http://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] connects the residues Cys138 and Cys161.  The disulfide bond can be seen in yellow in the <scene name='69/694222/1cpx_default/1'>original rotating figure</scene>.