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]] <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 it typically has been found pointing outward toward solution (GREEN LINK) 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 Tyr248 pointing toward the active site (GREEN LINK) 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 Zn (SUPERSCRIPT) 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 native conformation of Tyr248 in solution because none of the residues in the protein’s active site interact in the crystallographic packing (main article, 59, 60). Not only does Tyr248 point toward the active site, but in doing so, Tyr248 caps the hydrophobic binding pocket (GREEN LINK) 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>.