PDBsum entry 6tzh

Hydrolase

PDB id

6tzh

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Contents

			Protein chains

					354 a.a.

			Ligands

					ERF ×4


					GLY ×5


					PO4

			Waters ×238

PDB id:

6tzh

Links

Name:

Hydrolase

Title:

Adc-7 in complex with boronic acid transition state inhibitor s06015

Structure:

Beta-lactamase. Chain: a, b, c, d. Engineered: yes

Source:

Acinetobacter baumannii. Organism_taxid: 470. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.04Å

R-factor:

0.223

R-free:

0.254

Authors:

E.R.Fish,R.A.Powers,B.J.Wallar

Key ref:

E.Caselli et al. (2020). 1,2,3-Triazolylmethaneboronate: A Structure Activity Relationship Study of a Class of β-Lactamase Inhibitors against Acinetobacter baumannii Cephalosporinase. ACS Infect Dis, 6, 1965-1975. PubMed id: 32502340 DOI: 10.1021/acsinfecdis.0c00254

Date:

12-Aug-19

Release date:

24-Jun-20

PROCHECK

	Headers

	References

Protein chains

Q6DRA1 (Q6DRA1_ACIBA) - Beta-lactamase from Acinetobacter baumannii

Seq: Struc:					383 a.a. 354 a.a.

Key:

PfamA domain

Secondary structure



		Enzyme reactions

Enzyme class:

E.C.3.5.2.6 - beta-lactamase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Penicillin Biosynthesis and Metabolism

Reaction:

a beta-lactam + H2O = a substituted beta-amino acid

Cofactor:

Zn(2+)

DOI no: 10.1021/acsinfecdis.0c00254	ACS Infect Dis 6:1965-1975 (2020)
PubMed id: 32502340

1,2,3-Triazolylmethaneboronate: A Structure Activity Relationship Study of a Class of β-Lactamase Inhibitors against Acinetobacter baumannii Cephalosporinase.
E.Caselli, F.Fini, M.L.Introvigne, M.Stucchi, M.A.Taracila, E.R.Fish, K.A.Smolen, P.N.Rather, R.A.Powers, B.J.Wallar, R.A.Bonomo, F.Prati.

ABSTRACT

Boronic acid transition state inhibitors (BATSIs) are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific BATSIs bearing an amide side chain mimicking the β-lactam's amide side chain are an established and recognized synthetic strategy. Herein, we describe a new class of BATSIs where the amide group is replaced by a bioisostere triazole; these compounds were designed as molecular probes. To this end, a library of 26 α-triazolylmethaneboronic acids was synthesized and tested against the clinically concerning Acinetobacter-derived cephalosporinase, ADC-7. In steady state analyses, these compounds demonstrated K