Metallo-β-Lactamase Ian Desmond.

Slides:

Advertisements

Similar presentations

AP Jeopardy RXNs And bonds Monomers Protein Structure Thermo Name that structure Enzymes

Advertisements

From: Protein Data Bank PDB ID: 1B0E Kalus, W., Zweckstetter, M., Renner, C., Sanchez, Y., Georgescu, J., Grol, M., Demuth, D., Schumacher, R., Dony, C.,

Catalytic Strategies. Basic Catalytic Principles What is meant by the binding energy as it relates to enzyme substrate interactions? –free energy released.

Methods for detection β-lactamases Sarah Alharbi.

Biology 107 Macromolecules II September 9, Macromolecules II Student Objectives:As a result of this lecture and the assigned reading, you should.

Biology 107 Macromolecules II September 8, 2003.

1. Primary Structure: Polypeptide chain Polypeptide chain Amino acid monomers Peptide linkages Figure 3.6 The Four Levels of Protein Structure.

Proteins Structures Primary Structure.

Amino acid side chains stabilise the enzyme shape.

Protein Structure Lecture 2/26/2003. beta sheets are twisted Parallel sheets are less twisted than antiparallel and are always buried. In contrast, antiparallel.

The Nature of the Active Site Questions we want to ask: 1.Looking at the reactants and products, what type of reaction has occurred Hydrolysis, Condensation,

1 Chapter 3: Protein ZHOU Yong Department of Biology Xinjiang Medical University.

Supersecondary structures. Supersecondary structures motifs motifs or folds, are particularly stable arrangements of several elements of the secondary.

Topic 7.5 Proteins (AHL).

Chapter 3 Protein Structure and Function. Key Concepts Most cell functions depend on proteins. Amino acids are the building blocks of proteins. Amino.

Biochemical Overview on Amino Acids Structure and Protein Structure and Function Dr. Waheed Al-Harizi Medical Biochemistry Department College of Medicine.

PROTEINS C, H, O, N, (S) Polymers made from chains of amino acids 20 amino acids used Linked by a peptide bond.

Proteins and Amino Acids 1. Biological Functions of Proteins Facilitate biochemical reactions Structural support Storage and Transport Immune protection.

1.4 ENZYMES. Enzyme are _________________ catalysts.  Either tertiary or quaternary.  Names ususually end in ‘ase.’ CATALYST: substance that _____________.

Protein Structure Visualization By using Chime – a browser plugin Yuying Tian Information Visualization (Instructor: Dr. Chris North)

PROTEIN FUNCTIONS. PROTEIN FUNCTIONS (continued)

Proteins often consist of multiple domains –Usually different functions (eg. catalysis, regulation, targeting) –Often can be physically separated Non-covalent.

1 Chapter 12 Zinc  Lewis Acid and Gene Regulator Copyright © 2012 Elsevier Inc. All rights reserved.

Themes: Structure meets Function

Happy Monday! 9/16/2013 PQ & Journal—7.5 & 7.6 Test Wednesday, let’s boogy!

Protein Structure Primary - sequence of amino acids Secondary – folding into pleated sheets or alpha helix Tertiary – 3-D structure, completely folded.

Protein Structure  The structure of proteins can be described at 4 levels – primary, secondary, tertiary and quaternary.  Primary structure  The sequence.

Proteins pp Proteins Proteins are used for: Amino acids.

Lesson 13 – Enzyme Activity

Enzymes. Amino Acid Basic Structure Primary Structure.

Proteins Structure and Function. PROTEINS Proteins are essential to the structures and activities of life...

Protein Structure and Function. Proteins are organic compounds made from amino acids held together by peptide bonds.

Amino Acids. Amino acids are used in every cell of your body to build the proteins you need to survive. Amino Acids have a two-carbon bond: – One of the.

© SSER Ltd.. Proteins are huge three-dimensional molecules whose building blocks or monomers are the variety of different amino acids found in nature.

Functions Enzymes – organic catalysts Structural – skin, hair, muscle Antibodies Hormones.

Sample Problem 20.1 The Enzyme Active Site

The Chemical Biology of Human Metallo-β-Lactamase Fold Proteins

Carboxypeptidase Mechanism

Proteins: Secondary, Tertiary, Quaternary, and Denaturation

Protein structure is conceptually divided into four levels of organization Primary structure is the amino acid sequence of a protein's polypeptide chain.

IN SILICO ANALYSIS OF INHIBITOR AND SUBSTRATE BINDING SITE OF SERRAPEPTIDASE FROM SERRATIA MARCESCENS MTCC N.S.Kaviyarasi1, C.N.Prashantha 2, V.V.S.Suryanarayana3.

Protein Folding Notes.

Nestor O Concha, Beth A Rasmussen, Karen Bush, Osnat Herzberg

Enzymes Section 1.4.

Chapter 20 Enzymes and Vitamins

Protein Folding.

Protein Structure and Function

The Nature of the Active Site

Conformationally changed Stability

Study Question: What are enzymes?

Enzymes and Proteins.

Volume 87, Issue 2, Pages (October 1996)

Volume 3, Issue 12, Pages (December 1995)

Nestor O Concha, Beth A Rasmussen, Karen Bush, Osnat Herzberg

The construction of metal centers in proteins by rational design

Conformationally changed Stability

Ian Desmond and Jasmin Dipasupil

Volume 12, Issue 1, Pages (March 2004)

The Chemical Biology of Human Metallo-β-Lactamase Fold Proteins

Crystal Structure of Constitutive Endothelial Nitric Oxide Synthase

Volume 10, Issue 3, Pages (March 2003)

Edith Schlagenhauf, Robert Etges, Peter Metcalf Structure

T.R. Walsh Clinical Microbiology and Infection

Each antibody binds to a specific antigen; an interaction similar to a lock and key.

Volume 3, Issue 6, Pages (June 1995)

Volume 10, Issue 3, Pages (March 2003)

Presentation transcript:

Metallo-β-Lactamase Ian Desmond

Overveiw Metallo-β-Lactamases- enzymes that inactivate β-lactam antibiotics, by catalyzing the hydrolysis of the four-membered ring no clinically available inhibitors

General Structure Three classes of Metallo-β-Lactamases based on their amino acid sequences: B1, B2, B3 All classes possess: 1) one or two potential Zinc ion binding sites in the active site 2) similar αβ/βα fold

Class B1 Broad Spectrum Active with one or two Zn ions in active site Zn 1 site: 3 Histidine Zn 2 site: Asparagine-Cysteine-Histidine Effect of Zn binding: Binding of 2 Zn atoms for optimal hydrolysis Examples:Bc II, IMP- I, Ccr A, VIM, GIM, SPM-1

Class B2 High specificity for hydrolyzing carbapenems Aeromonas enzymes Zn 1 site: 2 Histidine, 1 Asparagine Zn 2 site: Asparagine-Cysteine-Histidine Effect of Zn binding: Binding of second Zn atom is inhibitory Catalytic Zn cofactor occupies the Zn 2 site Examples: Cph A, Sfh-1

Class B3 High specifi city for hydrolyzing cephalosporins Has a Tetrameric enzyme form (LI), all other forms are monomeric Zn 1 site: 3 Histidine Zn 2 site: Asparagine-Histidine-Histidine Effect of Zn binding: Binding of 2 Zn atoms for optimal hydrolysis Examples: LI, FEZ-1, Gob-1, CAU-1

Primary Structure their primary structures exhibit low degrees of sequence isology generally less than 43%

Secondary Structure two domains of roughly equivalent topology αβ/βα fold N-terminal domain=β1β2β3β4β5α1β6α2β7α3 C-terminal domain=β8β9β10β11α4β12α5

Secondary Structure

Protein Fold

Tertiary Structure Their three-dimensional structures show high degrees of similarity each domain contains ββββαβα motif. No significant sequence homology was found between the two motifs.

Quaternary Structure Zn-1 is coordinated to three histidines and a water molecule. Zn-2 interacts with a cysteine, an aspartic acid, and a histidine (BcII, IMP-1, and CcrA) or an aspartic acid and two histidines (for L1) and two water molecules in a trigonal pyramid. di-zinc form=one water molecule is bridged between the metal ions.

Active Site

Structure of Active Site active site is located at the bottom of a groove running between the two β sheets The four Zn2+ ligands are arranged in a distorted tetrahedral shape. Seven out of the nine strictly conserved residues are located in the active site: His88, Asp9O, Leull4, Hisl49, Glyl79, Asnl80 and His210.

Works Cited Images http://www.rcsb.org/pdb/explore/explore.do?structureId=2WRS http://jb.oxfordjournals.org/content/140/4/535.full Web Sites http://aac.asm.org/cgi/content/full/45/4/1254 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90352/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168685/ http://cmbi.bjmu.edu.cn/news/report/2010/pdf/ndm_7.pdf https://webmail.stedwards.edu/service/home/~/article1.pdf?auth=co&loc=en_US&id=46820&part=2 https://webmail.stedwards.edu/service/home/~/article2.pdf?auth=co&loc=en_US&id=46820&part=3 https://webmail.stedwards.edu/service/home/~/emboj00044-0024.pdf?auth=co&loc=en_US&id=46820&part=5 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC394593/pdf/emboj00044-0024.pdf