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Class B Beta- Lactamases

These class of beta lactamases basically contains Metallo beta lactamases or Metallo enzymes.


Metals play roles in approximately one-third of the known enzymes. Metals may be a co-factor or they may be incorporated into the molecule, and these are known as metalloenzymes. Amino Acids in peptide linkage posses groups that can form coordinate-covalent bonds with the metal atom. The free amino and carboxy group bind to the metal affecting the enzymes structure resulting in its active conformation . Metals main function is to serve in electron transfer. Many enzymes can serve as electrophiles and some can serve as nucleophilic groups. This versatility explains metals frequent occurrence in enzymes. Some metalloenzymes include hemoglobins, cytochromes, phosphotransferases, alcohol dehydrogenase, arginase, ferredoxin, and cytochrome oxidase.

Carboxypeptidase A is a zinc metalloenzyme that breaks peptide linkages in the digestion of proteins. The zinc ion that the enzyme contains in its active site plays a key role in that function.

Metalloenzymes can be regulated in several ways since they are such a diverse group. One way metalloenzymes are regulated is the pH level. The pH level can disrupt the electron flow that the metal would normally help facilitate. In this way the pH level could inhibit the overall effectiveness of the metalloenzyme.

Transition state analogs play a key role in the competitive inhibition of metalloenzymes because they mimic the structure of the substrates transition state in the reaction of enzyme and substrate.

Metalloenzymes such as the ones containing zinc can also be regulated by diet. The source of zinc in humans is almost entirely through diet. Without proper intake of metals such as zinc in a persons diet, the activity of the enzyme would be inhibited.


Metalloenzymes are proteins which function as an enzyme and contain metals that are tightly bound and always isolated with the protein. In proteins such as hemoglobins and cytochromes, the metal is Fe2+ or Fe3+, and it is part of the heme prosthetic group. In other metalloenzymes the metal is built into the structure of the enzyme molecule. The metal ion can not be removed with out destroying the structure of the enzyme. Metals built into the molecule include: most phosphotransferases, containing Mg2+; alcohol dehydrogenase, Zn2+; arginase, Mn2+; ferredoxin, Fe2+; and cytochrome oxidase, Cu2+ .

Metals are usually found in the active site of the enzyme. The metals resemble protons (H+) in that they are electrophiles that are able to accept an electron pair to form a chemical bond. In this aspect, metals may act as general acids to react with anionic and neutral ligands .

Metal's larger size relative to protons is compensated for by their ability to react with more than one ligand. Metals typically react with two, four, or six ligands. A ligand is whatever molecule the metal interacts with. If a metal is bound with two ligands it will form a linear complex. If the metal reacts with four ligands the metal will be set in the center of a square that is planer or it will form a tetrahedral structure, and when six ligands react, the metal sits in the center of an octahedron.

Amino acids in their peptide linkage in proteins possess groups with the ability to bind to the metal resulting in coordinate-covalent bonds. The free amino and carboxyl groups in a protein can bind to the metal and this may bind the protein to a specific, active conformation . The fact that metals bind to several ligands is important in that metals play a role in bringing remote parts of the amino acid sequence together and help establish an active conformation of the enzyme.

Zinc is the metal incorporated in carboxypeptidase A. The zinc atom serves as a metal ion catalyst and promotes hydrolysis. The substrate fits into the hydrophobic pocket in carboxypeptidase A and zinc binds to the carboxyl group of the substrate to help stabilize the enzyme-substrate complex. In this example the zinc ion acts a generalized acid and stabilizes the developing O- as water attacks the carbonyl.

Zinc can also perform a different role in enzymes like the role it performs in carbonic anhydrase. Here the metal binds H2O and makes it acidic enough to lose a proton and form a Zn-OH group. The zinc metal serves as a nucleophile to the substrate. Since zinc has the ability to act as an electrophile or as the source of a nucleophilic group it is incorporated and used by many enzymes

Function and Role:


A four-subunit molecule, containing a iron atom in each subunit, in which each subunit binds a single molecule of oxygen. Hemoglobin transports oxygen from the lungs to the capillaries of the tissue.


Cytochromes are integral membrane proteins. Cytochromes contain iron which serves to carry electrons between two segments of the electron-transport chain. The iron is reversibly oxidizable and serves as the actual electron acceptor for the cytochrome.


The Mg2+ atom serves again in electron transfer.

Alcohol Dehydrogenase

A zinc metalloenzyme with broad specificity. They oxidize a range of aliphatic and aromatic alcohols to their corresponding aldehydes and ketones using NAD+ as a coenzyme.


The metal atom of Mn2+ is used in electron transfer.


An electron transferring proteins involved in one-electron transfer processes.

Cytochrome Oxidase

The copper ions easily accommodate electron removed from a substrate and can just as easily transfer them to a molecule of oxygen


Carboxypeptidase A (CPA) is a zinc metalloenzyme that undergoes a large conformational change upon binding of the substrate that serves the purpose of bringing together the components of the active site. It is important to see that the zinc metal ion plays a key role in the catalytic process . Carboxypeptidase A is an exopeptidase which hydrolyzes the oligopeptides one at a time from the C-terminal end of the polypeptide chain. CPA is specific for large hydrophobic side chains while its closely related complimentary digestive enzyme, Carboxypeptidase B (CPB), is specific to basic residues. This complementary relationship between CPA and CPB is very similar to that of the closely related group of non-metalloenzymes of the digestive system, chymotrypsin and trypsin. However, chymotrypsin and trypsin are endopeptidases that catalyze the hydrolysis of non-terminal peptide bonds . As was stated CPA preferentially hydrolyzes peptides when the terminal residue is hydrophobic, either aromatic or branched aliphatic groups make favorable substituents. The binding is also stereospecific, as the side group must be in the L-configuration.