Carboxypeptidase A: Difference between revisions

1CPX’s most interesting distinction from other CPA proteins is that its crystallographic data revealed a different conformation of the Tyr248 residue [[Image:1CPX-Tyr248.png|thumb|Figure 2: Important Tyr248 residue of 1CPX pointing toward the hydrophobic binding pocket.]] <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>. Previous literature has suggested that the conserved Tyrosine residue among CPA proteins has been involved in an [https://en.wikipedia.org/wiki/Enzyme_catalysis#Induced_fit induced fit mechanism] because <scene name='69/694222/Tyr248_5cpa/1'>Tyr248 typically has been found pointing outward toward solution</scene> when a substrate is not bound to the enzyme (see [https://en.wikipedia.org/wiki/CPA3 3CPA]) <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>. However, 1CPX's crystallographic data shows <scene name='69/694222/Tyr248_1cpx/1'>Tyr248 pointing toward the active site</scene> without a substrate bound. Therefore, this denies the previously proposed induced fit mechanism for CPA proteins and suggests that Tyr 248 is a ligand to the catalytic Zinc in 1CPX <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>. Moreover, this data supports that this is the <scene name='69/694222/Tyr248_1cpx/1'>native conformation of Tyr248 in solution</scene> because none of the residues in the protein’s active site interact in the crystallographic packing <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>. Not only does Tyr248 point toward the active site, but in doing so, <scene name='69/694222/Tyr248_pointing_toward/2'>Tyr248 caps the hydrophobic binding pocket</scene> (blue) with its interactions with Ile247 and a hydrogen bond <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>. This point of view is able to clearly show how Tyr248 is thought to be a ligand with the catalytic Zinc.