The three-dimensional structure of VIM-31--a metallo-β-lactamase from Enterobacter cloacae in its native and oxidized form.

The metallo-β-lactamase VIM-31 differs from VIM-2 by only two Tyr224His and His252Arg substitutions. Located close to the active site, the Tyr224His substitution is also present in VIM-1, VIM-4, VIM-7 and VIM-12. The VIM-31 variant was reported in 2012 from Enterobacter cloacae and kinetically characterized.

GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.

A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam.

Kinetic and crystallographic studies of extended-spectrum GES-11, GES-12, and GES-14 β-lactamases.

GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low k(cat) values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1 to 3 amino acid substitutions that affect substrate specificity.

Effects and mechanisms of angiotensin II receptor blockade with telmisartan in a normotensive model of mesangioproliferative nephritis.

Background: Renoprotective actions of angiotensin receptor blockers are not well established in normotensive, low-grade proteinuric glomerular diseases. We examined the effect of low-dose telmisartan (LT) and high-dose telmisartan (HT) versus conventional antihypertensive therapy in the rat anti-Thy1.1 model of glomerulonephritis.

Broad antibiotic resistance profile of the subclass B3 metallo-β-lactamase GOB-1, a di-zinc enzyme.

The metallo-β-lactamase (MBL) GOB-1 was expressed via a T7 expression system in Escherichia coli BL21(DE3). The MBL was purified to homogeneity and shown to exhibit a broad substrate profile, hydrolyzing all the tested β-lactam compounds efficiently. The GOB enzymes are unique among MBLs due to the presence of a glutamine residue at position 116, a zinc-binding residue in all known class B1 and B3 MBL structures.

The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site.

Bacteria can defend themselves against beta-lactam antibiotics through the expression of class B beta-lactamases, which cleave the beta-lactam amide bond and render the molecule harmless. There are three subclasses of class B beta-lactamases (B1, B2, and B3), all of which require Zn2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-beta-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion.

Preliminary X-ray analysis of a human V(H) fragment at 1.8 A resolution.

Small antibody fragments are more useful than full-size antibodies for achieving efficient biodistribution. As a first step towards the design of a clinically desirable antibody fragment, the crystallization of a human V(H) fragment has been achieved. The fragment was derived from the single-chain antibody scFvM12, which recognizes a cancer-specific hypoglycosylated form of mucin.