advances-in-protein-chemistry

More documents

Recommendations

Info

Role of Matrix Metalloproteinases in Cancer Mohd. Afaque Ansari 1 , Sibhghatulla Shaikh 1 , Ghazala Muteeb 2 , Syed Mohd. Danish Rizvi 1 *, Shazi Shakil 3 , Aftab Alam 3 , Rashmi Tripathi 1 , Fauzia Ghazal 1 , Deboshree Biswas 1 , Mohammad Akram 4 , Ajijur Rehman 1 , Saeedut Zafar Ali 5 , Anil Kumar Pandey 3 and Ghulam Md Ashraf 6 1 Department of Biosciences, Integral University, Lucknow, India 2 Freelance researcher, Abu Dhabi, UAE 3 Department of Bio-engineering, Integral University, Lucknow, India 4 Department of Biology, Rabigh College of Science and Arts, King Abdulaziz University, Jeddah, Saudi Arabia-21589 5 Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India 6 King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia *Corresponding author: Dr. Syed Mohd. Danish Rizvi, Assistant Professor, Department of Biosciences, Integral University, Lucknow 226026, India, Tel: +91-8004702899; Fax: +91-522-2890809; E-mail: syedrizvi10@yahoo.com, shazibiotech@gmail.com Introduction Matrix metalloproteinases (MMPs) are endopeptidases which depend on zinc for their activity. They belong to the metzincin family of enzymes that codes for a highly conserved zinc binding motif. MMPs have a role in degrading all kinds of extracellular matrix proteins and can also act upon a number of bioactive molecules. These are also called matrixins. MMPs cleave cell surface receptors; they release apoptotic ligands like FAS ligand, and also mediate activation or inactivation of chemokine and cytokine [1]. MMPs effect many behavioral patterns of the cell; like its proliferation, differentiation, migration and apoptosis. In addition, they play a major role in angiogenesis and host defence. The first MMP was discovered when Jerome Gross and Charles Lapiere (1962) found out enzymatic activity during metamorphosis of the tadpole tail. They observed that the collagen triple helix degraded when the tadpole tail placed in collagen matrix metamorphosed [2]. Their suggestion was that the tadpole tissue produced a protease which was diffusible, but as EDTA could inhibit cleavage, it suggested an involvement of MMP. Released as an inactive proenzyme, MMPs are activated by factors which are regulated by TIMP (tissue inhibitors of matrix metalloproteinases). The endogenous inhibitor family of TIMP is formed by four enzymes. Brew et al., reported in 2010 that pathological conditions may develop due to imbalance in the levels of MMP and TIMP [3]. Various reports show that an increase in expression of MMPs leads to various inflammatory, malignant and degenerative diseases. Thus there is a possibility that inhibitors of MMPs have therapeutic value [4-6]. Structure The MMPs have three common domains, namely • The pro-peptide, which is responsible for keeping the enzyme in an inactive form. This domain contains “cysteine switch”- a unique and conserved cysteine residue that interacts with the zinc in the active site. Interaction with the zinc prevents binding and cleavage of the substrate. This domain has to be proteolytically cleaved in order to make the enzyme active. The cleavage is done intracellularly by furin or extracellularly by other MMPs or serine proteinases such as plasmin [7]. • The catalytic domain- the structural signature of which is the zinc binding motif. The Zn 2+ ion, bound by three histidine residues, forms the active site. The active site runs horizontally across the molecule as a shallow groove, and binds the substrate. • The hinge region- A flexible hinge or linker region which connects the catalytic domain to the C-terminal domain. Although this 75 amino acids long region and has no determinable structure, it is very important for the enzyme’s stability. • The hemopexin-like C-terminal domain-which is so named due to its sequence similarity to a serum protein, haemopexin. The polypeptide chain of this domain organizes into four β sheets. These β sheets or blades arrange themselves symmetrically around a central channel, resulting into a four-bladed β-propeller structure. The flat surface provided by this structure is believed to be involved in interactions between proteins and is a determinant of substrate specificity, for example TIMP, interacts with this site. However, this domain is not present in plants and nematodes. ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) are the two families of metzincin proteinases that are closely related to the MMPs. Mostly membrane-anchored and pericellular space functioning ADAMs play roles in fertilization, development, and cancer [8]. ADAMs perform their function in a nonproteolytic manner. The generally secreted and soluble ADAMTS enzymes, function during ECM assembly, ovulation, and cancer, and have a protease, a disintegrin, and one or more thrombospondin domains [9]. OMICS Group eBooks 004
MMPs are believed to remodel the ECM as they are capable of degrading ECM molecules. Likewise, MMPs may carry out significant functions during embryonic development as ECM remodelling is considered a critical part of tissue growth and morphogenesis. Additionally, MMPs also influence many cellular functions during development and normal physiology, for example: Figure 1: Modelled structure of the full-length pro MMP. The catalytic domain is shown in standard orientation. The pro-domain and the catalytic domain are taken from the experimental proMMP-3 catalytic domain structure, whereas the linker (blue spheres) and the haemopexin-like domain are taken from and attached as seen in the crystal structure of full-length MMP-1. The catalytic domain from the hinge residue, Pro107, onwards is given as a solid surface colored according to the electrostatic surface potential. In the centre of the active-site cleft running from left to right resides the catalytic zinc (pink half sphere, center). The pro-segment is shown as a yellow ribbon with its ordered segments only, that is with the first (only apparently separated) helix, the second helix, the connecting loop, the third helix and the switch loop (running across the catalytic zinc liganding it via the conserved Cys side chain, shown as a green CPK model), and the rocker arm (green color), which swings to the bottom left after activation cleavage. The haemopexin-like domain consisting of the four blades I to IV and viewed at its exit side is shown as a golden ribbon; the single calcium ion (blue sphere, back) located at the entry side (MMP-1) is shown together with the second calcium (central blue sphere) and the two chlorine ions (black spheres) found in the haemopexin-like domains of gelatinase A and MMP-13. (1) Allowing cell migration through degradation of ECM molecules; (2) Altering cellular behavior by changing ECM micro-environment; (3) Modulating the activity of biologically active molecules by direct cleavage, release from bound stores, or the modulating of the activity of their inhibitors. Figure 2: Modes of action of the matrix metalloproteinases. (A) MMPs may affect cell migration by changing the cells from an adhesive to non adhesive phenotype and by degrading the ECM. (B) MMPs may alter ECM microenvironment leading to cell proliferation, apoptosis, or morphogenesis. (C) MMPs may modulate the activity of biologically active molecules such as growth factors or growth factor receptors by cleaving them or releasing them from the ECM. (D) MMPs may alter the balance of protease activity by cleaving the enzymes or their inhibitors. OMICS Group eBooks 005
Page 1 and 2: www.esciencecentral.org/ebooks Adva
Page 3 and 4: Tyrosine Nitrated Proteins: Biochem
Page 5 and 6: [58-61]. Protein sulfhydryls [62] a
Page 7 and 8: 2. Souza JM, Daikhin E, Yudkoff M,
Page 9 and 10: Oligoclonality of the antibody resp
Page 11 and 12: The Recent Methodologies of Protein
Page 13 and 14: are due to altering protein activit
Page 15 and 16: Figure 6: At Domain Level, Protein
Page 17 and 18: Brownian Dynamics (BD) method Prote
Page 19 and 20: protein demonstrate the lowest ener
Page 21 and 22: Figure 12: Steps in Protein Prepara
Page 23 and 24: FlexServ The flexibility of protein
Page 25 and 26: 21. van der Kamp MW, Shaw KE, Woods
Page 27 and 28: Advances in Protein Thermodynamics
Page 29 and 30: 3. Fluorescence correlation spectro
Page 31 and 32: Figure 3: Molecular Chaperone (Top
Page 33 and 34: Figure 7: A Potherse is Consists of
Page 35 and 36: Figure 12: Residue Clusters with Mu
Page 37 and 38: Figure 16: Various Features at the
Page 39 and 40: Figure 21: Stability of protein str
Page 41: Advances in Protein Chemistry Chapt
Page 45 and 46: MMPs7 (Matrilysin, PUMP 1) A big ro
Page 47 and 48: MMP27 (MMP-22, C-MMP) mRNAs for MMP
Page 49 and 50: Signal transduction MMP production
Page 51 and 52: a | Active MMPs are generated throu
Page 53 and 54: Future Perspective Research into ne
Page 55 and 56: 56. Yonemura Y, Endo Y, Fujita H, K
Page 57 and 58: 126. López-Boado YS, Wilson CL, Ho
Page 59 and 60: Proteins and Peptides- Reemergence
Page 61 and 62: Figure 3: Schematic representation
Page 63 and 64: Figure 6: Different mechanisms of c
Page 65 and 66: [30,33]. Clinical trials with autoi
Page 67 and 68: Therapeutic Proteins Figure 9: Mole
Page 69 and 70: Coming years will witness increasin
Page 71 and 72: Advances in Protein Chemistry Chapt
Page 73 and 74: purification methodology and laid t
Page 75 and 76: An overview of various purification
Page 77 and 78: Affinity chromatography (AC): The p
Page 79 and 80: molecules such as proteins. Further
Page 81 and 82: However, for proteins with poor sol
Page 83 and 84: The schematic of an HPLC instrument
Page 85 and 86: » Denaturation of all proteins giv
Page 87 and 88: Advances in Protein Chemistry Chapt
Page 89 and 90: the biological society access to th
Page 91 and 92: identifier, since a single macromol
Page 93 and 94:
Furthermore, the initial models for
Page 95 and 96:
evaluation [78], Whatcheck [79] and
Page 97 and 98:
corresponding to gaps in the FR ali
Page 99 and 100:
programming (IP) problem based on t
Page 101 and 102:
or almost the entire target. - Temp
Page 103 and 104:
3.2.1.10 Geno3D http://geno3d-pbil.
Page 105 and 106:
80. Laskowski RA, MacArthur MW, Mos
Page 107 and 108:
165. Zhang Y, Kolinski A, Skolnick
Page 109 and 110:
Advances in Protein Chemistry Chapt
Page 111 and 112:
Figure 1: Biochemical and biophysic
Page 113 and 114:
equilibrium an equilibrium concentr
Page 115 and 116:
for virtually all macromolecules to
Page 117 and 118:
egion) for estimating fraction or p
Page 119 and 120:
etween proteins in living cells. It
Page 121 and 122:
pre-requisite in understanding how
Page 123 and 124:
82. Rodger A, Marrington R, Roper D
Page 125 and 126:
New Peptide Based Therapeutic Appro
Page 127 and 128:
ability to selectively target cells
Page 129 and 130:
24 amino acid extracellular domain
Page 131 and 132:
separation efficiency. However, use
Page 133 and 134:
the peptides through acetylation an
Page 135 and 136:
63. Mesiano AJ, Beckman EJ, Russell
Page 137 and 138:
Antimicrob Agents Chemother 49: 330
Page 139 and 140:
Protein Detection Techniques Dennis
Page 141 and 142:
technique has been applied to the i
Page 143 and 144:
involves placing our protein of int
show all

advances-in-protein-chemistry

Create successful ePaper yourself

Delete template?

Save as template?