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Comparative analysis of human matrix metalloproteinases: Emerging therapeutic targets in diseases.

Jaiswal A, Chhabra A, Malhotra U, Kohli S, Rani V - Bioinformation (2011)

Bottom Line: This initial screening can help to reduce time and cost of testing and experimentation in laboratory.Thus, a plausible grouping of disease responsive MMPs that might be considered as promising clinical targets may be done.This study can be used as a fundamental approach to characterize, analyze and screen large protein families for the identification of signature patterns.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, NOIDA- 201307, Uttar Pradesh, India.

ABSTRACT
The identification of specific target proteins for any diseased condition involves extensive characterization of the potentially involved proteins. Members of a protein family demonstrating comparable features may show certain unusual features when implicated in a pathological condition. Advancements in the field of computational biology and the use of various bioinformatics tools for analysis can aid researchers to comprehend their system of work in primary stages of research. This initial screening can help to reduce time and cost of testing and experimentation in laboratory. Human matrix metalloproteinase (MMP) family of endopeptidases is one such family of 23 members responsible for the remodeling of extracellular matrix (ECM) by degradation of the ECM proteins. Though their role has been implicated in various pathological conditions such as arthritis, atherosclerosis, cancer, liver fibrosis, cardio-vascular and neurodegenerative disorders, little is known about the specific involvement of members of the large MMP family in diseases. A comparative in silico characterization of the MMP protein family has been carried out to analyze their physico-chemical, secondary structural and functional properties. Based on the observed patterns of occurrence of atypical features, we hypothesize that cysteine rich and highly thermostable MMPs might be key players in diseased conditions. Thus, a plausible grouping of disease responsive MMPs that might be considered as promising clinical targets may be done. This study can be used as a fundamental approach to characterize, analyze and screen large protein families for the identification of signature patterns.

No MeSH data available.


Related in: MedlinePlus

Computation of aliphatic index by ExPASy's ProtParam tool. Thealiphatic index indicates the thermostability of proteins. MMP-23 was found tobe the most thermostable MMP with a high aliphatic index of 83.59.
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Figure 3: Computation of aliphatic index by ExPASy's ProtParam tool. Thealiphatic index indicates the thermostability of proteins. MMP-23 was found tobe the most thermostable MMP with a high aliphatic index of 83.59.

Mentions: Other physico-chemical parameters also signify the behavior of MMPs indifferent conditions (see Table 3(a) and Table 3(b) see supplementary material). pIvalues for majority of MMPs (MMP-7, 12, 14, 15, 16, 19, 20, 21, 23, 24, 25, 27and 28) lie in the alkaline range (pH>7) while for the others, (MMP-1, 2, 3, 8,9, 10, 11, 13, 17 and 26) it falls in the acidic range (pH<7). In addition to this,the instability index classifies MMP - 1, 2, 3, 7, 8, 10, 12, 13, 16, 19, 20, 26and 27 as stable (Instability index <40) and remaining as unstablemetalloproteinases (Instability index <40) (Figure 2). Furthermore, aliphaticindex, signifying the relative volume of protein occupied by aliphatic sidechains helps to study thermo stable properties of an enzyme. It is found to spanwithin a range of 61.09 to 83.59 (Figure 3). Stability of human MMPs in asmall range suggests their unstable nature over wide temperature range, thoughMMP-23 is observed as the most thermostable MMP. Moreover, highextinction coefficients are observed for MMP- 2, 15, 16, 21, 24 and 28, whichis correlated with a high concentration of lysine, tryptophan and tyrosineresidues in the sequence and may be useful in protein-protein and proteinligandinteraction studies in solution. Hydrophobicity values range from -0.6720 of MMP-19 (most hydrophilic) to 0.4615 of MMP-14 (mosthydrophobic).


Comparative analysis of human matrix metalloproteinases: Emerging therapeutic targets in diseases.

Jaiswal A, Chhabra A, Malhotra U, Kohli S, Rani V - Bioinformation (2011)

Computation of aliphatic index by ExPASy's ProtParam tool. Thealiphatic index indicates the thermostability of proteins. MMP-23 was found tobe the most thermostable MMP with a high aliphatic index of 83.59.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3064848&req=5

Figure 3: Computation of aliphatic index by ExPASy's ProtParam tool. Thealiphatic index indicates the thermostability of proteins. MMP-23 was found tobe the most thermostable MMP with a high aliphatic index of 83.59.
Mentions: Other physico-chemical parameters also signify the behavior of MMPs indifferent conditions (see Table 3(a) and Table 3(b) see supplementary material). pIvalues for majority of MMPs (MMP-7, 12, 14, 15, 16, 19, 20, 21, 23, 24, 25, 27and 28) lie in the alkaline range (pH>7) while for the others, (MMP-1, 2, 3, 8,9, 10, 11, 13, 17 and 26) it falls in the acidic range (pH<7). In addition to this,the instability index classifies MMP - 1, 2, 3, 7, 8, 10, 12, 13, 16, 19, 20, 26and 27 as stable (Instability index <40) and remaining as unstablemetalloproteinases (Instability index <40) (Figure 2). Furthermore, aliphaticindex, signifying the relative volume of protein occupied by aliphatic sidechains helps to study thermo stable properties of an enzyme. It is found to spanwithin a range of 61.09 to 83.59 (Figure 3). Stability of human MMPs in asmall range suggests their unstable nature over wide temperature range, thoughMMP-23 is observed as the most thermostable MMP. Moreover, highextinction coefficients are observed for MMP- 2, 15, 16, 21, 24 and 28, whichis correlated with a high concentration of lysine, tryptophan and tyrosineresidues in the sequence and may be useful in protein-protein and proteinligandinteraction studies in solution. Hydrophobicity values range from -0.6720 of MMP-19 (most hydrophilic) to 0.4615 of MMP-14 (mosthydrophobic).

Bottom Line: This initial screening can help to reduce time and cost of testing and experimentation in laboratory.Thus, a plausible grouping of disease responsive MMPs that might be considered as promising clinical targets may be done.This study can be used as a fundamental approach to characterize, analyze and screen large protein families for the identification of signature patterns.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, NOIDA- 201307, Uttar Pradesh, India.

ABSTRACT
The identification of specific target proteins for any diseased condition involves extensive characterization of the potentially involved proteins. Members of a protein family demonstrating comparable features may show certain unusual features when implicated in a pathological condition. Advancements in the field of computational biology and the use of various bioinformatics tools for analysis can aid researchers to comprehend their system of work in primary stages of research. This initial screening can help to reduce time and cost of testing and experimentation in laboratory. Human matrix metalloproteinase (MMP) family of endopeptidases is one such family of 23 members responsible for the remodeling of extracellular matrix (ECM) by degradation of the ECM proteins. Though their role has been implicated in various pathological conditions such as arthritis, atherosclerosis, cancer, liver fibrosis, cardio-vascular and neurodegenerative disorders, little is known about the specific involvement of members of the large MMP family in diseases. A comparative in silico characterization of the MMP protein family has been carried out to analyze their physico-chemical, secondary structural and functional properties. Based on the observed patterns of occurrence of atypical features, we hypothesize that cysteine rich and highly thermostable MMPs might be key players in diseased conditions. Thus, a plausible grouping of disease responsive MMPs that might be considered as promising clinical targets may be done. This study can be used as a fundamental approach to characterize, analyze and screen large protein families for the identification of signature patterns.

No MeSH data available.


Related in: MedlinePlus