PDBsum entry 6dwf

Hydrolase

PDB id: 6dwf

Contents

Protein chains

(+ 0 more) 223 a.a.

(+ 0 more) 163 a.a.

Waters ×1636

PDB id:

6dwf

Name:

Hydrolase

Title:

Crystal structure of complex of bbki mutant, l55r with bovine trypsin

Structure:

Cationic trypsin. Chain: a, b, c, d, e, f. Fragment: residues 24-246. Synonym: beta-trypsin. Kunitz-type inihibitor. Chain: g, h, i, j, k, l. Fragment: residues 19-181. Engineered: yes. Mutation: yes

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Bauhinia bauhinioides. Organism_taxid: 166014. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.94Å R-factor: 0.197 R-free: 0.223

Authors:

M.Li,A.Wlodawer,A.Gustchina

Key ref:

M.Li et al. (2019). Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes. Acta Crystallogr D Struct Biol, 75, 56-69. PubMed id: 30644845 DOI: 10.1107/S2059798318016492

Date:

26-Jun-18 Release date: 30-Jan-19

Protein chains

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Protein chains

Q6VEQ7  (Q6VEQ7_BAUBA) -  Kunitz-type inihibitor from Bauhinia bauhinioides

Seq: 193 a.a.

Struc: 163 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

DOI no: 10.1107/S2059798318016492

Acta Crystallogr D Struct Biol 75:56-69 (2019)

PubMed id: 30644845

Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes.

M.Li, J.Srp, A.Gustchina, Z.Dauter, M.Mares, A.Wlodawer.

ABSTRACT

Structures of a recombinant Kunitz-type serine protease inhibitor from Bauhinia bauhinioides (BbKI) complexed with bovine trypsin were determined in two crystal forms. The crystal structure with the L55R mutant of BbKI was determined in space group P6₄ at 1.94 Å resolution and that with native BbKI in the monoclinic space group P2₁ at 3.95 Å resolution. The asymmetric unit of the latter crystals contained 44 independent complexes, thus representing one of the largest numbers of independent objects deposited in the Protein Data Bank. Additionally, the structure of the complex with native BbKI was determined at 2.0 Å resolution from P6₄ crystals isomorphous to those of the mutant. Since BbKI has previously been found to be a potent inhibitor of the trypsin-like plasma kallikrein, it was also tested against several tissue kallikreins. It was found that BbKI is a potent inhibitor of human tissue kallikrein 4 (KLK4) and the chymotrypsin-like human tissue kallikrein 7 (KLK7). Structures of BbKI complexed with the catalytic domain of human plasma kallikrein were modeled, as well as those with KLK4 and KLK7, and the structures were analyzed in order to identify the interactions that are responsible for inhibitory potency.