Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family
TL;DR: The environment and coordination of the two zinc ions in A. proteolytica aminopeptidase strongly support the view that the two metal ions constitute a co-catalytic unit and play equivalent roles during catalysis.
About: This article is published in Structure.The article was published on 1994-04-01. It has received 226 citations till now. The article focuses on the topics: Aminopeptidase & Exopeptidase.
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TL;DR: The authors present here a classification and structure/function analysis of native metal sites based on these functions, and the coordination chemistry of metalloprotein sites and the unique properties of a protein as a ligand are briefly summarized.
Abstract: For present purposes, a protein-bound metal site consists of one or more metal ions and all protein side chain and exogenous bridging and terminal ligands that define the first coordination sphere of each metal ion. Such sites can be classified into five basic types with the indicated functions: (1) structural -- configuration (in part) of protein tertiary and/or quaternary structure; (2) storage -- uptake, binding, and release of metals in soluble form: (3) electron transfer -- uptake, release, and storage of electrons; (4) dioxygen binding -- metal-O{sub 2} coordination and decoordination; and (5) catalytic -- substrate binding, activation, and turnover. The authors present here a classification and structure/function analysis of native metal sites based on these functions, where 5 is an extensive class subdivided by the type of reaction catalyzed. Within this purview, coverage of the various site types is extensive, but not exhaustive. The purpose of this exposition is to present examples of all types of sites and to relate, insofar as is currently feasible, the structure and function of selected types. The authors largely confine their considerations to the sites themselves, with due recognition that these site features are coupled to protein structure at all levels. In themore » next section, the coordination chemistry of metalloprotein sites and the unique properties of a protein as a ligand are briefly summarized. Structure/function relationships are systematically explored and tabulations of structurally defined sites presented. Finally, future directions in bioinorganic research in the context of metal site chemistry are considered. 620 refs.« less
2,242 citations
TL;DR: Zinc enzymology is, compared to some other current areas of metallobiochemistry, a maturing field, but in addition to further developments of structure-function relationships it has also provided a number of surprising new results and ideas in the last few years.
Abstract: Zinc enzymology is, compared to some other current areas of metallobiochemistry, a maturing field, but in addition to further developments of structure-function relationships it has also provided a number of surprising new results and ideas in the last few years. In fact, the number of studies makes it impossible to provide a comprehensive review of the recent literature on zinc enzymology here, and the authors therefore focus on those zinc enzymes for which structure-function relationships are possible on the basis of structural and biochemical data. This means that, with a few exceptions, only zinc enzymes for which NMR or crystal structures are available are included here. Another seemingly simple, yet experimentally sometimes complex issue concerns the choice of which metalloenzyme is a zinc enzyme. Since there is in principle no difference in chemical catalysis by low-affinity compared to high-affinity metal sites, some of these enzymes are also included in this article, especially if they are or have been discussed as zinc enzymes, or are active with zinc. 552 refs.
1,257 citations
TL;DR: The influence of zinc on quaternary protein structure has led to the identification of a fourth type of zinc binding site, protein interface, which is formed from ligands supplied from amino acid residues residing in the binding surface of two proteins.
Abstract: Zinc is known to be indispensable to growth and development and transmission of the genetic message. It does this through a remarkable mosaic of zinc binding motifs that orchestrate all aspects of metabolism. There are now nearly 200 three dimensional structures for zinc proteins, representing all six classes of enzymes and covering a wide range of phyla and species. These structures provide standards of reference for the identity and nature of zinc ligands in other proteins for which only the primary structure is known. Three primary types of zinc sites are apparent from examination of these structures: structural, catalytic and cocatalytic. The most common amino acids that supply ligands to these sites are His, Glu, Asp and Cys. In catalytic sites zinc generally forms complexes with water and any three nitrogen, oxygen and sulfur donors with His being the predominant amino acid chosen. Water is always a ligand to such sites. Structural zinc sites have four protein ligands and no bound water molecule. Cys is the preferred ligand in such sites. Cocatalytic sites contain two or three metals in close proximity with two of the metals bridged by a side chain moiety of a single amino acid residue, such as Asp, Glu or His and sometimes a water molecule. Asp and His are the preferred amino acids for these sites. No Cys ligands are found in such sites. The scaffolding of the zinc sites is also important to the function and reactivity of the bound metal. The influence of zinc on quaternary protein structure has led to the identification of a fourth type of zinc binding site, protein interface. In this case zinc sites are formed from ligands supplied from amino acid residues residing in the binding surface of two proteins. The resulting zinc site usually has the coordination properties of a catalytic or structural zinc binding site.
699 citations
Cites background from "Crystal structure of Aeromonas prot..."
...Zinc binding sites in enzymes: catalytic (thermolysin (Matthews 1988)), structural (alcohol dehydrogenase (Eklund & Branden 1987)), cocatalytic (Aeromonas proteolytica aminopeptidase (Chevrier et al. 1994))....
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TL;DR: A zinc binding template in protein crystal structures is derived from observing the sequence pattern of the zinc ligands and residues that provide elecs, and identifying conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site.
Abstract: The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.
406 citations
TL;DR: Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure.
329 citations
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TL;DR: A set of simple and physically motivated criteria for secondary structure, programmed as a pattern‐recognition process of hydrogen‐bonded and geometrical features extracted from x‐ray coordinates is developed.
Abstract: For a successful analysis of the relation between amino acid sequence and protein structure, an unambiguous and physically meaningful definition of secondary structure is essential. We have developed a set of simple and physically motivated criteria for secondary structure, programmed as a pattern-recognition process of hydrogen-bonded and geometrical features extracted from x-ray coordinates. Cooperative secondary structure is recognized as repeats of the elementary hydrogen-bonding patterns “turn” and “bridge.” Repeating turns are “helices,” repeating bridges are “ladders,” connected ladders are “sheets.” Geometric structure is defined in terms of the concepts torsion and curvature of differential geometry. Local chain “chirality” is the torsional handedness of four consecutive Cα positions and is positive for right-handed helices and negative for ideal twisted β-sheets. Curved pieces are defined as “bends.” Solvent “exposure” is given as the number of water molecules in possible contact with a residue. The end result is a compilation of the primary structure, including SS bonds, secondary structure, and solvent exposure of 62 different globular proteins. The presentation is in linear form: strip graphs for an overall view and strip tables for the details of each of 10.925 residues. The dictionary is also available in computer-readable form for protein structure prediction work.
14,077 citations
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Abstract: The MOLSCRIPT program produces plots of protein structures using several different kinds of representations. Schematic drawings, simple wire models, ball-and-stick models, CPK models and text labels can be mixed freely. The schematic drawings are shaded to improve the illusion of three dimensionality. A number of parameters affecting various aspects of the objects drawn can be changed by the user. The output from the program is in PostScript format.
13,971 citations
TL;DR: This chapter considers the parameters that are required for an adequate description of a polypeptide chain and the mathematical method of utilizing these parameters for calculating the coordinates of all the atoms in a suitable frame of reference so that all the interatomic distances, and bond angles, can be calculated and their consequences worked out.
Abstract: Publisher Summary This chapter deals with the recent developments regarding the description and nature of the conformation of proteins and polypeptides with special reference to the stereochemical aspects of the problem. This chapter considers the parameters that are required for an adequate description of a polypeptide chain. This chapter focuses the attention on what may be called “internal parameters”—that is, those which can be defined in terms of the relationships among atoms or units that form the building blocks of the polypeptide chains. This chapter also provides an account of the mathematical method of utilizing these parameters for calculating the coordinates of all the atoms in a suitable frame of reference, so that all the interatomic distances, and bond angles, can be calculated and their consequences worked out. This chapter observes conformations in amino acids, peptides, polypeptides, and proteins.
2,802 citations
TL;DR: A model building and refinement system is described for use with a Vector General 3400 display that has been used to assist in difference Fourier map interpretation at medium and high resolution, and to build a protein molecule into a multiple isomorphous replacement phased electron density map.
Abstract: A model building and refinement system is described for use with a Vector General 3400 display. The system allows the user to build models using guide atoms and angles to arrive at the final conformation. It has been used to assist in difference Fourier map interpretation at medium and high resolution, and to build a protein molecule into a multiple isomorphous replacement phased electron density map.
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