Structural and sequence-based classification of glycoside hydrolases.

Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the mucosal surfaces of the host nasopharynx and upper airway. Through a combination of virulence-factor activity and an ability to evade the early components of the host immune response, this organism can spread from the upper respiratory tract to the sterile regions of the lower respiratory tract, which leads to pneumonia. In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause disease.

The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease.

Standard conformations for the canonical structures of immunoglobulins

http://www.chemie.uni-muenchen.de/ac/kluefers/homepage/L/bac/ca_2004.pdf

Synthetic analogues relevant to the structure and function of zinc enzymes.

Hyaluronic acid (HA) is a high molecular weight biopolysacharide, discovered in 1934, by Karl Meyer and his assistant, John Palmer in the vitreous of bovine eyes. Hyaluronic acid is a naturally occurring biopolymer, which has important biological functions in bacteria and higher animals including humans. It is found in most connective tissues and is particularly concentrated in synovial fluid, the vitreous fluid of the eye, umbilical cords and chicken combs. It is naturally synthesized by a class of integral membrane protein s called hyaluronan synthases, and degraded by a family of enzymes called hyaluronidases. This review describes metabolisms, different physi - ological and pathological functions, basic pharmacological properties, and the clinical use of hyaluronic acid.

/pdf/hyaluronic-acid-hyaluronan-a-review-55rx73a414.pdf

Hyaluronic acid (hyaluronan): a review

The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease.

Pneumococcal Virulence Factors: Structure and Function

Streptococcus pneumoniae hyaluronate lyase (spnHL) is a pathogenic bacterial spreading factor and cleaves hyaluronan, an important constituent of the extracellular matrix of connective tissues, through an enzymatic β-elimination process, different from the hyaluronan degradation by hydrolases in animals. The mechanism of hyaluronan binding and degradation was proposed based on the 1.56 A resolution crystal structure, substrate modeling and mutagenesis studies on spnHL. Five mutants, R243V, N349A, H399A, Y408F and N580G, were constructed and their activities confirmed our mechanism hypothesis. The important roles of Tyr408, Asn349 and His399 in enzyme catalysis were proposed, explained and confirmed by mutant studies. The remaining weak enzymatic activity of the H399A mutant, the role of the free carboxylate group on the glucuronate residue, the enzymatic behavior on chondroitin and chondroitin sulfate, and the small activity increase in the N580G mutant were explained based on this mechanism. A possible function of the C-terminal β-sheet domain is to modulate enzyme activity through binding to calcium ions.

/pdf/structural-basis-of-hyaluronan-degradation-by-streptococcus-34eienp2t3.pdf

Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase.

2. Cofactor dependent Saccharomyces cerevisiae phosphoglycerate mutase . . . . . . . . . . . . . . . . 265 2.1. Structural aspects of Saccharomyces cerevisiae phosphoglycerate mutase . . . . . . . . . . 265 2.2. Mechanism of catalysis of the S. cerevisiae dPGM . . . . . . . . . . . . . . . . . . . . . . . . . . 270 2.3. Structural comparison of dPGM with other enzymes . . . . . . . . . . . . . . . . . . . . . . . . 270 2.3.1. Structural comparison of S. cerevisiae dPGM with 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271 2.3.2. Structural comparison of S. cerevisiae dPGM with acid phosphatase . . . . . . . 272 2.3.3. Overall comparison of active sites of dPGM, Fru26P2ase, and AcPase . . . . . 273

Structure, function, and evolution of phosphoglycerate mutases: comparison with fructose-2,6-bisphosphatase, acid phosphatase, and alkaline phosphatase

https://pure.mpg.de/pubman/item/item_599541_5/component/file_1479195/599541.pdf

Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase. Structures of complexes with the substrate.

Comparison of the binuclear metalloenzymes diphosphoglycerate-independent phosphoglycerate mutase and alkaline phosphatase: their mechanism of catalysis via a phosphoserine intermediate.

Mark J. Jedrzejas

Papers

Pneumococcal Virulence Factors: Structure and Function

Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase.

Structure, function, and evolution of phosphoglycerate mutases: comparison with fructose-2,6-bisphosphatase, acid phosphatase, and alkaline phosphatase

Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase. Structures of complexes with the substrate.

Comparison of the binuclear metalloenzymes diphosphoglycerate-independent phosphoglycerate mutase and alkaline phosphatase: their mechanism of catalysis via a phosphoserine intermediate.