1BTX
Episelection: Novel Ki ~Nanomolar Inhibitors of Serine Proteases Selected by Binding or Chemistry on an Enzyme Surface
Summary for 1BTX
| Entry DOI | 10.2210/pdb1btx/pdb |
| Related | 1btw 1btz |
| Related PRD ID | PRD_000389 |
| Descriptor | BETA-TRYPSIN, N-(tert-butoxycarbonyl)-L-alanyl-N-[(1S)-5-amino-1-(diethoxyboranyl)pentyl]-L-valinamide, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | tripeptideboronate ethyl ester 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 | 24525.46 |
| Authors | Stroud, R.M.,Katz, B.A.,Finer-Moore, J. (deposition date: 1995-05-17, release date: 1995-10-15, Last modification date: 2024-11-13) |
| 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 Cited by 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: 7599119DOI: 10.1021/bi00026a008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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