Abstract:
:The generation of neutralizing antibodies by peptide immunization is dependent on achieving conformational compatibility between antibodies and native protein. Consequently, approaches are needed for developing conformational mimics of protein neutralization sites. We replace putative main-chain hydrogen bonds (NH --> O=CRNH) with a hydrazone link (N-N=CH-CH(2)CH(2)) and scan constrained peptides for fit with neutralizing monoclonal antibodies (MAbs). To explore this approach, a V3 MAb 58.2 that potently neutralizes T-cell lab-adapted HIV-1(MN) was used to identify a cyclic peptide, [JHIGPGR(Aib)F(D-Ala)GZ]G-NH(2) (loop 5), that binds with >1000-fold higher affinity than the unconstrained peptide. NMR structural studies suggested that loop 5 stabilized beta-turns at GPGR and R(Aib)F(D-Ala) in aqueous solvent implying considerable conformational mimicry of a Fab 58.2 bound V3 peptide determined by X-ray crystallography [Stanfield, R. L. et al. (1999) Structure 142, 131-142]. Rabbit polyclonal antibodies (PAbs) generated to loop 5 but not to the corresponding uncyclized peptide bound the HIV-1(MN) envelope glycoprotein, gp120. When individual rabbit antisera were scanned with linear and cyclic peptides, further animal-to-animal differences in antibody populations were characterized. Loop 5 PAbs that most closely mimicked MAb 58.2 neutralized HIV-1(MN) with similar potency. These results demonstrate the remarkable effect that conformation can have on peptide affinity and immunogenicity and identify an approach that can be used to achieve these results. The implications for synthetic vaccine and HIV-1 vaccine research are discussed.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Cabezas E,Wang M,Parren PW,Stanfield RL,Satterthwait ACdoi
10.1021/bi0003691subject
Has Abstractpub_date
2000-11-28 00:00:00pages
14377-91issue
47eissn
0006-2960issn
1520-4995pii
bi0003691journal_volume
39pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::F-STOP is a microtubule-associated protein that stabilizes microtubules in a calmodulin (CaM)-dependent manner. All members of the stable tubule only polypeptide (STOP) family have a central domain that contains nearly identical multiple repeats, and a CaM binding motif is present in multiple copies within this domain...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034746w
更新日期:2003-10-07 00:00:00
abstract::During the past decade, there has been much debate about the enormous catalytic rate enhancement observed in enzymatic reactions involving carbanion intermediates. Our recent theoretical study has demonstrated the importance of the short strong hydrogen bond (SSHB) in the enzymatic reactions. Nevertheless, other recen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0255118
更新日期:2002-04-23 00:00:00
abstract::It is well-known, but little understood, that the nucleotide sequences between phased A(4-6)-tracts (at 10-11 bp intervals) have only a slight effect on overall curvature. To explore this phenomenon, we have examined the gel-migration properties of sequences containing both A-tracts as well as G-tracts (i.e., sequence...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020662w
更新日期:2003-05-06 00:00:00
abstract::The inhibition of phosphorylase kinase catalytic activity by 0.1 M neutral salts was predicted by the Hofmeister series of anions. The site of action of the salts was determined by the following evidence to be on the phosphorylase kinase molecule directly, rather than on its protein substrate. (1) Nonactivated kinase ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00665a022
更新日期:1976-10-05 00:00:00
abstract::Four murine myeloma immunoglobulins, A4, A47N, U61, and E109, have been studied for their binding affinities with inulin and a series of oligosaccharides derived from inulin. The results indicate that the combining site of these immunoglobulins shows highest complementarity for a trifructofuranosyl sequence (A4 and A4...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00636a005
更新日期:1977-08-23 00:00:00
abstract::Cytochrome P450 (P450) 3A4 is the most abundant human P450 and oxidizes a diversity of substrates, including various drugs, steroids, carcinogens, and macrolide natural products. In some reactions, positive cooperativity has been reported in microsomal studies. Flavonoids, e.g., 7,8-benzoflavone (alpha-naphthoflavone,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962359z
更新日期:1997-01-14 00:00:00
abstract::It has been shown (Poole et al., 1991) that deletion of residues 44-49 from the sequence of staphylococcal nuclease (E43 SNase) results in an enzyme (E43 delta SNase) that is significantly more active than D43 SNase, an enzyme that differs from the wild-type enzyme by deletion of a single methylene group. In addition,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00229a006
更新日期:1991-04-16 00:00:00
abstract::Myosin belongs to the family of motor proteins. Its interaction with actin coupled with hydrolysis of ATP is the molecular basis of muscle contraction. The head segment of myosin, called subfragment 1 (S1), contains the distinct binding sites for ATP and actin and responsible for the ATPase activity. The rate-limiting...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952565r
更新日期:1996-04-09 00:00:00
abstract::Blood coagulation is initiated by Ca(2+)-dependent binding of coagulation factor VIIa (FVIIa) to its cofactor, tissue factor (TF). The TF:FVIIa complex activates factors IX and X, ultimately leading to the formation of thrombin and the coagulation of blood. FVII consists of an N-terminal gamma-carboxyglutamic-acid-con...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980522f
更新日期:1998-07-28 00:00:00
abstract::Phosphoenolthiopyruvate, the analogue of phosphoenolpyruvate in which the bridging oxygen of the phosphate ester is replaced by sulfur, has been synthesized from methyl acrylate and dimethyl (chlorothio)phosphonate. The compound is a substrate for alkaline phosphatase, pyruvate kinase, enolase, and phosphoenolpyruvate...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00404a038
更新日期:1988-02-23 00:00:00
abstract::Rod outer segment membrane guanylate cyclase (ROS-GC) transduction system is a central component of the Ca(2+)-sensitive phototransduction machinery. The system is composed of two parts: Ca(2+) sensor guanylate cyclase activating protein (GCAP) and ROS-GC. GCAP senses Ca(2+) impulses and inhibits the cyclase. This ope...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034025x
更新日期:2003-05-20 00:00:00
abstract::Fesselin is a proline-rich actin-binding protein that was isolated from avian smooth muscle. Fesselin bundles actin and accelerates actin polymerization by facilitating nucleation. We now show that this polymerization of actin can be regulated by Ca(2+)-calmodulin. Fesselin was shown to bind to immobilized calmodulin ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0487490
更新日期:2004-11-02 00:00:00
abstract::Mammalian cGMP- and cAMP-dependent protein kinase show considerable similarity in amino acid sequence, although they specifically bind different cyclic nucleotides. Results of cGMP analogue binding experiments, combined with modeling of the cGMP binding sites by analogy to the structure of the homologous catabolite ge...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00440a059
更新日期:1989-07-11 00:00:00
abstract::The fungal neurotoxin alpha-cyclopiazonic acid (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic indole tetramic acid scaffold, is assembled by a three enzyme pathway CpaS, CpaD, and CpaO in Aspergillus sp. We recently characterized the first pathway-specific enzyme CpaS, a hybrid two module poly...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi901597j
更新日期:2009-11-24 00:00:00
abstract::The iron-chelating peptide vibriobactin of the pathogenic Vibrio cholerae is assembled by a four-subunit nonribosomal peptide synthetase complex, VibE, VibB, VibH, and VibF, using 2,3-dihydroxybenzoate and L-threonine as precursors to two 2,3-dihydroxyphenyl- (DHP-) methyloxazolinyl groups in amide linkage on a norspe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010937s
更新日期:2001-09-04 00:00:00
abstract::The human translin protein binds a variety of sequences (chromosomal breakpoint consensus sequences, their sequence variants, as well as nonbreakpoint sequences such as simple AT and GC repeats) at nanomolar protein concentration when short single strands ( approximately 20-30mers) are used as DNA targets. The protein...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026378m
更新日期:2002-12-24 00:00:00
abstract::The egg jelly that encapsulates amphibian eggs is essential for fertilization, but its molecular composition and roles remain largely unknown. We identified a calcium-dependent lectin from the pentraxin superfamily in the egg jelly coat from the South American burrowing frog, Lepidobatrachus laevis. This lectin, jeltr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035314o
更新日期:2003-11-11 00:00:00
abstract::The structure of the specific phosphate binding loop (P-loop) of bovine protein tyrosine phosphatase (BPTP) is very similar to that present in high M(r) PTPases. Site-directed mutagenesis was used to explore the role of several conserved residues involved in forming the P-loop of BPTP. Thus, Ser-19 and Ser-43 were ind...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9605651
更新日期:1996-10-22 00:00:00
abstract::A detailed structural study of the prokaryotic sodium/galactose transporter (vSGLT) from Vibrio parahaemolyticus using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy reveals stepwise increases in alpha-helicity upon binding of sodium and D-galactose. These increases in helicity correlat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi025692d
更新日期:2002-06-25 00:00:00
abstract::The cofactor product of the aromatic amino acid hydroxylases, 4a-hydroxy-6(R)-tetrahydrobiopterin, requires dehydration before tetrahydrobiopterin can be regenerated by dihydropteridine reductase. Carbinolamine dehydration occurs nonenzymatically, but the reaction is also catalyzed by 4a-hydroxytetrahydropterin dehydr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00017a011
更新日期:1995-05-02 00:00:00
abstract::When they are translated, steroid receptors are assembled into a multiprotein complex containing hsp90, p23, an immunophilin, and often some hsp70. Some of the receptors, such as that for progesterone, have nuclear localization signals that are functional in the absence of hormone, and they move into the nucleus where...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970648x
更新日期:1997-06-24 00:00:00
abstract::Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011389l
更新日期:2001-12-11 00:00:00
abstract::The flexibility of individual amino acid side chains of pancreatic phospholipase A2 in aqueous and micellar solutions was studied with deuterium nuclear magnetic resonance (2H NMR). Bovine pancreatic phospholipase A2 was selectively deuterated at the aromatic ring systems of Trp-3 and Phe-5 and porcine pancreatic phos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00334a029
更新日期:1985-06-18 00:00:00
abstract::In halophilic archaea the photophobic response is mediated by the membrane-embedded 2:2 photoreceptor/-transducer complex SRII/HtrII, the latter being homologous to the bacterial chemoreceptors. Both systems bias the rotation direction of the flagellar motor via a two-component system coupled to an extended cytoplasmi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501160q
更新日期:2015-01-20 00:00:00
abstract::We have used site-directed mutagenesis to alter the [Fe-S] cluster composition of Escherichia coli dimethyl sulfoxide (DMSO) reductase (DmsABC). The electron-transfer subunit (DmsB) of this enzyme contains 16 Cys residues arranged in 4 groups (I-IV) which provide ligands to 4 [4Fe-4S] clusters [Cammack, R., & Weiner, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00098a003
更新日期:1991-08-27 00:00:00
abstract::The Vmax/Km (microM -1 min -1.) for bovine factor X activation by bovine factor IXa alpha, in the presence of sufficient [Ca2+] to saturate the initial reaction rate, was 0.007. When factor IXa beta was substituted for factor IXa alpha in this reaction, the Vmax/Km decreased to 0.001, suggesting that factor IXa alpha ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00286a007
更新日期:1983-08-16 00:00:00
abstract::Release of neurotransmitter from synaptic vesicles requires the Ca2+/phospholipid-binding protein synaptotagmin 1. There is considerable evidence that cooperation between the tandem C2 domains of synaptotagmin is a requirement of regulated exocytosis; however, high-resolution structural evidence for this interaction h...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701651k
更新日期:2007-11-13 00:00:00
abstract::Efforts toward the development of RNA-based drug leads have been challenging because of the complexity and dynamic nature of RNA structures as therapeutic targets. The transactivation response (TAR) RNA and cognate Tat protein of HIV have long been recognized as promising antiviral targets, and recent works have ident...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00325
更新日期:2015-06-16 00:00:00
abstract::Atrazine chlorohydrolase (AtzA) from Pseudomonas sp. ADP initiates the metabolism of the herbicide atrazine by catalyzing a hydrolytic dechlorination reaction to produce hydroxyatrazine. Sequence analysis revealed AtzA to be homologous to metalloenzymes within the amidohydrolase protein superfamily. AtzA activity was ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020415s
更新日期:2002-12-03 00:00:00
abstract::Base excision repair (BER) is the major corrective pathway for most spontaneous, oxidative, and alkylation DNA base and sugar damage. X-ray cross-complementing 1 (XRCC1) has been suggested to function at nearly every step of this repair process, primarily through direct protein-protein interactions. Using whole cell e...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051161o
更新日期:2005-11-01 00:00:00