1BTW

Episelection: novel KI ~nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface

Summary for 1BTW

• Entry DOI: 10.2210/pdb1btw/pdb
• Related: 1btx 1btz
• Related PRD ID: PRD_000388
• Descriptor: BETA-TRYPSIN, N-(tert-butoxycarbonyl)-L-alanyl-N-{(1S)-5-ammonio-1-[hydroxy(3-hydroxypropoxy)boranyl]pentyl}-L-valinamide, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: tripeptideboronate 1, 3-propanediol monoester-inhibited, serine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 24528.44

Authors

Stroud, R.M.,Katz, B.A.,Finer-Moore, J. (deposition date: 1995-05-17, release date: 1995-10-15, Last modification date: 2024-10-23)

Primary citation

Katz, B.A.,Finer-Moore, J.,Mortezaei, R.,Rich, D.H.,Stroud, R.M.
Episelection: novel Ki approximately nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface.
Biochemistry, 34:8264-8280, 1995

PubMed Abstract: A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection.

PubMed: 7599119
DOI: 10.1021/bi00026a008

Experimental method

X-RAY DIFFRACTION (1.7 Å)