Hyaluronan Binding and Degradation byStreptococcus agalactiae Hyaluronate Lyase

Li, Songlin; Jedrzejas, Mark J.

doi:10.1074/jbc.m106634200

Cited by 88 publications

(110 citation statements)

References 41 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…The structures of the Ch and ChS complexes with the pneumococcal HL enzyme fully support the notion that the degradation of Ch and ChS proceeds via the same mechanism as proposed for the degradation of hyaluronan and termed the proton acceptance and donation mechanism (see Introduction) (11,27,28). The interactions of the Ch/ChS substrates mirror the essential interactions of the enzyme with HA, whose degradation was studied in more detail.…”

Section: Mechanism Of S Pneumoniae Hyaluronate Lyase Catalysis and Asupporting

confidence: 54%

“…Structural determinations have confirmed the homology of streptococcal HLs (11,19), CLs from Flavobacterium heparinum (17) and Proteus vulgaris (20) and have additionally included the more distantly related alginate lyase from Sphingomonas (21) in the superfamily. In each case, the catalytic domains, containing incomplete ␣/␣ toroids, bear strong structural similarity.…”

mentioning

confidence: 81%

“…Complex Formation, Crystallization, and Diffraction Data Collection-The wild-type, H399A, and Y408F mutant forms of S. pneumoniae HL were produced as previously reported (11,55) and chondroitin sulfates were obtained by co-crystallization. The hanging drop vapor diffusion method was employed (56), and equal volumes (1 l each) of the enzyme, 50 mM chondroitin solution (in 10 mM Tris-HCl), and reservoir solution were used.…”

Section: Methodsmentioning

confidence: 99%

“…The enzyme can be found in two forms, associated with bacterium through the linkage described above and in a cell-free form released by the action of sortase enzymes (2,9,10). The four HL domains are an Nterminal carbohydrate binding domain, followed by a spacer domain, the catalytic domain, and finally the C-terminal domain, which modulates access to the catalytic cleft of the enzyme transversing the catalytic domain (7,8,11). The fulllength molecule readily degrades when produced in a recombinant form, probably by an autocatalytic process, leaving the two C-terminal domains as a stable derivative, resistant to further degradation (2,12).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Structures of Streptococcus pneumoniae Hyaluronate Lyase in Complex with Chondroitin and Chondroitin Sulfate Disaccharides

Rigden

Jedrzejas²

2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Streptococcus pneumoniae hyaluronate lyase is a surface enzyme of this Gram-positive bacterium. The enzyme degrades hyaluronan and chondroitin/chondroitin sulfates by cleaving the ␤1,4-glycosidic linkage between the glycan units of these polymeric substrates. This degradation helps spreading of this bacterial organism throughout the host tissues and facilitates the disease process caused by pneumococci. The mechanism of this degradative process is based on ␤-elimination, is termed proton acceptance and donation, and involves selected residues of a well defined catalytic site of the enzyme. The degradation of hyaluronan alone is thought to proceed through a processive mode of action. The structures of complexes between the enzyme and chondroitin as well as chondroitin sulfate disaccharides allowed for the first detailed insights into these interactions and the mechanism of action on chondroitins. This degradation of chondroitin/chondroitin sulfates is nonprocessive and is selective for the chondroitin sulfates only with certain sulfation patterns. Chondroitin sulfation at the 4-position on the nonreducing site of the linkage to be cleaved or 2-sulfation prevent degradation due to steric clashes with the enzyme. Evolutionary studies suggest that hyaluronate lyases evolved from chondroitin lyases and still retained chondroitin/chondroitin sulfate degradation abilities while being specialized in the degradation of hyaluronan. The more efficient processive degradation mechanism has come to be preferred for the unsulfated substrate hyaluronan.

show abstract

Section: Mechanism Of S Pneumoniae Hyaluronate Lyase Catalysis and Asupporting

confidence: 54%

mentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Structures of Streptococcus pneumoniae Hyaluronate Lyase in Complex with Chondroitin and Chondroitin Sulfate Disaccharides

Rigden

Jedrzejas²

2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both the homologous enzymes (68% similarity) are initially expressed as 118/111-kDa and 107-kDa proteins, respectively, which are subsequently autodegraded from the N-terminal region and finally stabilized as 92-kDa (SagHL) and 89-kDa (SpnHL) proteins for which crystal structures are also available (10 -20). Crystal structures of both the HLs suggest that they are similar in whole structure architecture, and the active site geometry except for the spacer domain that is only present in SagHL (18). Although no calcium binding sites are observed on these enzymes,theirenzymaticactivitiesarereportedtobecalciumdependent (3,14,21).…”

mentioning

confidence: 96%

Insights into the Mechanism of Action of Hyaluronate Lyase

Akhtar

Krishnan

Bhakuni

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hyaluronate lyases (HLs) cleave hyaluronan and certain other chondroitin/chondroitin sulfates. Although native HL from Streptococcus agalactiae is composed of four domains, it finally stabilizes after autocatalytic conversion as a 92-kDa enzyme composed of the N-terminal spacer, middle ␣-, and C-terminal domains. These three domains are independent folding/unfolding units of the enzyme. Comparative structural and functional studies using the enzyme and its various fragments/domains suggest a relatively insignificant role of the N-terminal spacer domain in the 92-kDa enzyme. Functional studies demonstrate that the ␣-domain is the catalytic domain. However, independently it has a maximum of only about 10% of the activity of the 92-kDa enzyme, whereas its complex with the C-terminal domain in vitro shows a significant enhancement (about 6-fold) in the activity. It has been previously proposed that the C-terminal domain modulates the enzymatic activity of HLs. In addition, one of the possible roles for calcium ions was suggested to induce conformational changes in the enzyme loops, making HL more suitable for catalysis. However, we observed that calcium ions do not interact with the enzyme, and its role actually is in modulating the hyaluronan conformation and not in the functional regulation of enzyme.

show abstract

Streptococcal Hyaluronate Lyase Reveals the Presence of a Structurally Significant CH⋅⋅⋅O Hydrogen Bond

Moore

Migues

Schaefer

et al. 2013

Chemistry A European J

View full text Add to dashboard Cite

Carbon-donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5-1.0 kcal mol(-1) ) that are difficult to detect, and thus their roles in the structure and functionality of chemical systems often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second-order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing αHelix 3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of αHelix 3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of αHelix 3 observed from experiment. A strongly correlated motion between αHelix 3 and αHelices 2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just αHelix 3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena.

show abstract

Hyaluronan Binding and Degradation byStreptococcus agalactiae Hyaluronate Lyase

Cited by 88 publications

References 41 publications

Structures of Streptococcus pneumoniae Hyaluronate Lyase in Complex with Chondroitin and Chondroitin Sulfate Disaccharides

Structures of Streptococcus pneumoniae Hyaluronate Lyase in Complex with Chondroitin and Chondroitin Sulfate Disaccharides

Insights into the Mechanism of Action of Hyaluronate Lyase

Streptococcal Hyaluronate Lyase Reveals the Presence of a Structurally Significant CH⋅⋅⋅O Hydrogen Bond

Contact Info

Product

Resources

About