1CPS

STRUCTURAL COMPARISON OF SULFODIIMINE AND SULFONAMIDE INHIBITORS IN THEIR COMPLEXES WITH ZINC ENZYMES

Summary for 1CPS

• Entry DOI: 10.2210/pdb1cps/pdb
• Descriptor: CARBOXYPEPTIDASE A, ZINC ION, S-(2-CARBOXY-3-PHENYLPROPYL)THIODIIMINE-S-METHANE, ... (4 entities in total)
• Functional Keywords: hydrolase(c-terminal peptidase)
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00730
• Total number of polymer chains: 1
• Total formula weight: 34748.19

Authors

Cappalonga, A.M.,Alexander, R.S.,Christianson, D.W. (deposition date: 1992-02-18, release date: 1993-10-31, Last modification date: 2024-10-30)

Primary citation

Cappalonga, A.M.,Alexander, R.S.,Christianson, D.W.
Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes.
J.Biol.Chem., 267:19192-19197, 1992

PubMed Abstract: The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl) methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A has been determined at 2.25-A resolution by x-ray crystallographic methods. This is the first example of a sulfodiimine-containing inhibitor binding to a zinc enzyme, and the structure of the enzyme-inhibitor complex reveals that the tetrahedral sulfodiimine group coordinates to the active site zinc ion in unidentate fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is also within hydrogen bonding distance to active site base Glu-270; presumably, the sulfodiimine is ionized and accepts a hydrogen bond from protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen bond from Arg-127, and the inhibitor binds as a possible analogue of the tetrahedral transition state (or intermediate) in a promoted water pathway for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode observed in this enzyme-inhibitor complex is reminiscent of that observed in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase II, and the structural features of sulfodiimine- and sulfonamide-zinc interactions exhibit important similarities among recently determined structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc in each structure, and these nitrogens are engaged in hydrogen bond interactions with neighboring enzyme residues.

PubMed: 1527041

Experimental method

X-RAY DIFFRACTION (2.25 Å)