15.4 What Kinds of Covalent Modific

15.4 What Kinds of Covalent Modification Regulate the Activity of Enzymes? 461
substrate sequence has an alanine residue where serine occurs in the PKA target se-
quence; Ala is sterically similar to serine but lacks a phosphorylatable OH group.
When these PKA regulatory subunits bind cAMP, they undergo a conformational
change and dissociate from the catalytic (C) subunits, and the active site of PKA is free
to bind and phosphorylate its targets. In other protein kinases, the pseudosubstrate
sequence involved in intrasteric control and the kinase domain are part of the same
polypeptide chain. In these cases, binding of an allosteric effector (like cAMP) in-
duces a conformational change in the protein that releases the pseudosubstrate se-
quence from the active site of the kinase domain.
The abundance of many protein kinases in cells is an indication of the great impor-
tance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase
genes have been recognized in yeast, and 868 putative protein kinase genes have been
identified in the human genome. Tyrosine kinases (protein kinases that phosphorylate
Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases).
Tyrosine kinases are components of signaling pathways involved in cell–cell communi-
cation (see Chapter 32).
Phosphorylation Is Not the Only Form of Covalent Modification
That Regulates Protein Function
Several hundred different chemical modifications of proteins have been dis-
covered thus far, ranging from carboxylation (addition of a carboxyl group),
acetylation (addition of an acetyl group, see Figure 29.30), prenylation (see
Figure 9.23), and glycosylation (see Figures 7.32–7.39) to covalent attachment
of a polypeptide to the protein (addition of ubiquitin to free amino groups on
proteins; see Figure 31.8), to name just a few. A compilation of known protein
modifications can be found in RESID, the European Bioinformatics Institute
online database (http://www.ebi.ac.uk/RESID/). Only a small number of these co-
valent modifications are used to achieve metabolic regulation through reversible
conversion of an enzyme between active and inactive forms. Table 15.3 presents a few
examples.
+ cAMP
cAMP cAMP
cAMP cAMP
+ 2
C C
C R R R R
R2C2
inactive R2–(cAMP)4
ANIMATED FIGURE 15.10 Cyclic
AMP–dependent protein kinase (also known as
PKA) is a 150- to 170-kD R2C2 tetramer in mam-
malian cells. The two R (regulatory) subunits bind
cAMP (KD  3 -
108 M); cAMP binding releases
the R subunits from the C (catalytic) subunits.
C subunits are enzymatically active as monomers.
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Reaction Amino Acid Side Chain Reaction (see figure indicated)
Adenylylation Tyrosine Transfer of AMP from ATP to Tyr-OH
(Figure 25.16)
Uridylylation Tyrosine Transfer of UMP from UTP to Tyr-OH
(Figure 25.17)
ADP-ribosylation Arginine Transfer of ADP-ribose from NAD to
Arg (Figure 25.8)
Methylation Glutamate Transfer of methyl group from
S-adenosylmethionine to Glu
-carboxyl group
Oxidation-reduction Cysteine (disulfide) Reduction of Cys-S−S-Cys to
Cys-SH HS-Cys (Figure 21.27)
TABLE 15.3 Additional Examples of Regulation by Covalent Modification

Kết quả (Việt) 1:

15.4 những gì loại của cộng hoá trị sửa đổi điều chỉnh hoạt động của các enzym? 461bề mặt dãy có một dư lượng alanine nơi serine xảy ra trong PKA mục tiêu se-quence; Ala là sterically tương tự như serine nhưng thiếu một nhóm OH phosphorylatable.Khi những subunits quy định PKA ràng buộc trại, họ trải qua một conformationalthay đổi và chia rẻ từ subunits (C) chất xúc tác, và các trang web hoạt động của PKA là miễn phíđể ràng buộc và phosphorylate mục tiêu của mình. Trong các protein kinase, pseudosubstratetrình tự tham gia vào intrasteric kiểm soát và kinase miền là một phần của cùng mộtpolypeptide chuỗi. Trong những trường hợp này, ràng buộc của một effector allosteric (như trại) tại -duces là một thay đổi conformational của protein mà bản phát hành pseudosubstrate se -quence từ các trang web hoạt động của tên miền kinase.Sự phong phú của nhiều protein kinase trong tế bào là một dấu hiệu của impor lớn-tance của phosphorylation protein trong di động quy định. Chính xác 113 protein kinasegen đã được công nhận trong nấm men, và 868 giả định protein kinase gen đãđược xác định trong bộ gen của con người. Tyrosine kinase (protein kinase mà phosphorylateDư lượng TYR) xảy ra chỉ trong các sinh vật đa bào (nấm men đã không tyrosine kinase). Tyrosine kinase là thành phần của tín hiệu con đường tham gia vào tế bào-tế bào communi-cation (xem chương 32).Phosphorylation không phải là hình thức duy nhất của cộng hoá trị sửa đổi Đó quy định chức năng ProteinSeveral hundred different chemical modifications of proteins have been dis-covered thus far, ranging from carboxylation (addition of a carboxyl group),acetylation (addition of an acetyl group, see Figure 29.30), prenylation (seeFigure 9.23), and glycosylation (see Figures 7.32–7.39) to covalent attachmentof a polypeptide to the protein (addition of ubiquitin to free amino groups onproteins; see Figure 31.8), to name just a few. A compilation of known proteinmodifications can be found in RESID, the European Bioinformatics Instituteonline database (http://www.ebi.ac.uk/RESID/). Only a small number of these co-valent modifications are used to achieve metabolic regulation through reversibleconversion of an enzyme between active and inactive forms. Table 15.3 presents a fewexamples.+ cAMPcAMP cAMPcAMP cAMP+ 2C CC R R R RR2C2inactive R2–(cAMP)4ANIMATED FIGURE 15.10 CyclicAMP–dependent protein kinase (also known asPKA) is a 150- to 170-kD R2C2 tetramer in mam-malian cells. The two R (regulatory) subunits bindcAMP (KD  3 - 108 M); cAMP binding releasesthe R subunits from the C (catalytic) subunits.C subunits are enzymatically active as monomers.See this figure animated at www.cengage.com/login.Reaction Amino Acid Side Chain Reaction (see figure indicated)Adenylylation Tyrosine Transfer of AMP from ATP to Tyr-OH(Figure 25.16)Uridylylation Tyrosine Transfer of UMP from UTP to Tyr-OH(Figure 25.17)ADP-ribosylation Arginine Transfer of ADP-ribose from NAD toArg (Figure 25.8)Methylation Glutamate Transfer of methyl group from S-adenosylmethionine to Glu -carboxyl groupOxidation-reduction Cysteine (disulfide) Reduction of Cys-S−S-Cys to Cys-SH HS-Cys (Figure 21.27)TABLE 15.3 Additional Examples of Regulation by Covalent Modification