PDBsum entry 4kts

Hydrolase/hydrolase inhibitor

PDB id: 4kts

Contents

Protein chains

223 a.a.

14 a.a.

Ligands

PEG

Metals

_CA

Waters ×349

PDB id:

4kts

Name:

Hydrolase/hydrolase inhibitor

Title:

Bovine trypsin in complex with microviridin j at ph 8.5

Structure:

Cationic trypsin. Chain: a. Synonym: beta-trypsin, alpha-trypsin chain 1, alpha-trypsin chain 2. Microviridin. Chain: b. Engineered: yes

Source:

Bos taurus. Bovine,cow,domestic cattle,domestic cow. Organism_taxid: 9913. Other_details: pancreatic trypsin. Chain a. Microcystis aeruginosa mrc. Organism_taxid: 507735. Gene: mdna. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.30Å R-factor: 0.107 R-free: 0.128

Authors:

F.Quitterer,M.Groll,C.Hertweck,E.Dittmann

Key ref:

A.R.Weiz et al. (2014). Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions. Angew Chem Int Ed Engl, 53, 3735-3738. PubMed id: 24591244 DOI: 10.1002/anie.201309721

Date:

21-May-13 Release date: 02-Apr-14

Protein chain

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Protein chain

B2G3C8  (B2G3C8_MICAE) -  Microviridin from Microcystis aeruginosa MRC

Seq: 49 a.a.

Struc: 13 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

DOI no: 10.1002/anie.201309721

Angew Chem Int Ed Engl 53:3735-3738 (2014)

PubMed id: 24591244

Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions.

A.R.Weiz, K.Ishida, F.Quitterer, S.Meyer, J.C.Kehr, K.M.Müller, M.Groll, C.Hertweck, E.Dittmann.

ABSTRACT

Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed.